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Background To report our experience utilizing a multidisciplinary clinic (MDC) at Indiana University (IU) since the publication of the International Germ Cell Cancer Collaborative Group (IGCCCG), and to compare our overall survival (OS) to that of the National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results (SEER) Program. Patients and methods We conducted a retrospective analysis of all patients with metastatic germ-cell tumor (GCT) seen at IU from 1998 to 2014. A total of 1611 consecutive patients were identified, of whom 704 patients received an initial evaluation by our MDC (including medical oncology, pathology, urology and thoracic surgery) and started first-line chemotherapy at IU. These 704 patients were eligible for analysis. All patients in this cohort were treated with cisplatin–etoposide-based combination chemotherapy. We compared the progression-free survival (PFS) and OS of patients treated at IU with that of the published IGCCCG cohort. OS of the IU testis cancer primary cohort (n = 622) was further compared with the SEER data of 1283 patients labeled with ‘distant' disease. The Kaplan–Meier method was used to estimate PFS and OS. Results With a median follow-up of 4.4 years, patients with good, intermediate, and poor risk disease by IGCCCG criteria treated at IU had 5-year PFS of 90%, 84%, and 54% and 5-year OS of 97%, 92%, and 73%, respectively. The 5-year PFS for all patients in the IU cohort was 79% [95% confidence interval (CI) 76% to 82%]. The 5-year OS for the IU cohort was 90% (95% CI 87% to 92%). IU testis cohort had 5-year OS 94% (95% CI 91% to 96%) versus 75% (95% CI 73% to 78%) for the SEER ‘distant' cohort between 2000 and 2014, P-value Conclusion The MDC approach to GCT at high-volume cancer center associated with improved OS outcomes in this contemporary dataset. OS is significantly higher in the IU cohort compared with the IGCCCG and SEER ‘distant' cohort.

It is important to assess the prevalence of hypogonadism and to identify the correlation between hypogonadism and cancer treatment with quality of life (QoL) in germ cell tumor (GCT) survivors. This is a single-center, non-randomized, prospective observational study in GCT survivors 18–50 years of age previously treated with surgery and chemotherapy (S+C) or surgery alone (S). Patients completed a validated QoL questionnaire at baseline, 3, and 6 months. Patients received supplemental testosterone as clinically indicated. Mean QoL scores were compared between two treatment groups (S+C vs. S) and within each group between survivors with hypogonadism (serum testosterone level

PURPOSE: This review summarizes the recommendations for the prophylaxis of acute and delayed nausea and vomiting induced by multiple-day chemotherapy, high-dose chemotherapy, and breakthrough nausea and vomiting as agreed at the MASCC/ESMO Antiemetic Guidelines update meeting in Copenhagen in June 2015.METHODS: A systematic literature search using PubMed from January 01, 2009 through January 06, 2015 with a restriction to papers in English was conducted.RESULTS: There were three phase III randomized trials in patients undergoing high-dose chemotherapy and stem cell transplant and eight single arm non-randomized clinical studies (single in patients undergoing transplantation and one in patients receiving multiple-day chemotherapy treatment). We used a total of two randomized clinical trials in this guideline update. For patients receiving treatment for breakthrough chemotherapy-induced nausea and vomiting, a phase III randomized trial investigating the use of olanzapine versus metoclopramide in patients receiving highly emetogenic chemotherapy and a second single arm study looking at the effectiveness of olanzapine were identified.CONCLUSIONS: It was concluded that for patients receiving high-dose chemotherapy with stem cell transplant, a combination of a 5-HT3 receptor antagonist with dexamethasone and aprepitant (125 mg orally on day 1 and 80 mg orally on days 2 to 4) is recommended before chemotherapy. For patients undergoing multiple-day chemotherapy-induced nausea and vomiting, a 5-HT3 receptor antagonist, dexamethasone, and aprepitant, are recommended before chemotherapy for the prophylaxis of acute emesis and delayed emesis. For patients experiencing breakthrough nausea and vomiting, the available evidence suggests the use of 10 mg oral olanzapine, daily for 3 days. Mild to moderate sedation in this patient population (especially elderly patients) is a potential problem with this agent.

Purpose Aprepitant, a 5-HT3 receptor antagonist (5HT3-RA), and dexamethasone are standard antiemetic therapy for prevention of single-day, cisplatin-induced nausea and vomiting. We conducted a double-blind, placebo-controlled phase III cross-over study that compared aprepitant to placebo combined with standard antiemetic prophylaxis (a 5HT3-RA and dexamethasone) in patients receiving 5 days of cisplatin combination chemotherapy for testicular cancer. Patients and Methods Patients receiving two consecutive identical courses of a 5-day cisplatin-based chemotherapy were randomly assigned to aprepitant 125 mg on day 3 and 80 mg per day on days 4 through 7 or to placebo with the initial course and crossover to the opposite treatment with the second course. The primary objective was complete response (CR). Secondary end points were emetic episodes (acute and delayed), nausea measurement based on a visual analog scale (VAS), and patient-stated preference after the second study cycle. Results In all, 71 patients were screened for the study and 69 were evaluable. Thirty-five patients were randomly assigned to receive aprepitant and 34 to receive placebo for the first course. Forty-two percent achieved CR with aprepitant compared with 13% with placebo (P < .001). Eleven patients (16.2%) had at least one emetic episode during the aprepitant cycle versus 32 patients (47.1%) with placebo. Thirty-eight patients preferred the aprepitant cycle whereas 11 preferred placebo (P < .001). There was no statistical difference in VAS for nausea, but it was numerically superior with aprepitant. There was no toxicity with aprepitant compared with placebo. Conclusion There was a significant improvement in CR rate with aprepitant combined with a 5HT3-RA and dexamethasone. Patient preference strongly favored the aprepitant cycle.

10079Background: Prior studies have shown that around 12% to 16% Germ Cell Tumour (GCT) survivors can have subnormal serum testosterone level as well as up to 15% reported decreased health related ...

Objective To examine adolescent and young adult (AYA) testicular cancer survivors’ subjective understanding of the impact of cancer in adolescence and young adulthood, with a particular emphasis on romantic and sexual relationships.

Purpose Controversy arises regarding the optimal management of patients with nonseminomatous germ cell tumor (NSGCT) who achieve a serologic and radiographic complete remission (CR) to systemic chemotherapy. Some authors recommend postchemotherapy retroperitoneal lymph node dissection (PC-RPLND), whereas others omit surgery and observe these patients. In an attempt to address this question, we report the long-term follow-up of patients treated at Indiana University who were observed without PC-RPLND. Patients and Methods This is a retrospective analysis of patients with NSGCT who achieved a CR to first-line chemotherapy and were monitored without further therapy. CR was defined as normalization of serum tumor markers and resolution of radiographic disease (residual mass < 1 cm). Results One hundred forty-one patients were identified. Five patients (4%) had less than 2 years of follow-up. After a median follow-up of 15.5 years, 12 patients (9%) experienced relapse. Of these 12 patients, eight patients currently have no evidence of disease (NED), and four patients died of disease. The estimated 15-year recurrence-free survival (RFS) and cancer-specific survival rates were 90% and 97%, respectively. The estimated 15-year RFS for good-risk patients (n = 109) versus intermediate- or poor-risk patients (n = 32) was 95% and 73% (P = .001), respectively. Six patients (4%) experienced recurrence in the retroperitoneum, of whom two patients died of disease. Five patients had late relapse (range, 3 to 13 years), including two patients in the retroperitoneum. All five patients currently have NED. Conclusion Patients obtaining a CR after first-line chemotherapy can be safely observed without PC-RPLND. Relapses are rare and potentially curable with further treatment.

BACKGROUND Metastatic testicular tumors that have not been successfully treated by means of initial chemotherapy are potentially curable with salvage chemotherapy. METHODS We conducted a retrospective review of 184 consecutive patients with metastatic testicular cancer that had progressed after they received cisplatin-containing combination chemotherapy. We gave 173 patients two consecutive courses of high-dose chemotherapy consisting of 700 mg of carboplatin per square meter of body-surface area and 750 mg of etoposide per square meter, each for 3 consecutive days, and each followed by an infusion of autologous peripheral-blood hematopoietic stem cells; the other 11 patients received a single course of this treatment. In 110 patients, cytoreduction with one or two courses of vinblastine plus ifosfamide plus cisplatin preceded the high-dose chemotherapy. RESULTS Of the 184 patients, 116 had complete remission of disease without relapse during a median follow-up of 48 months (range, 14 to 118). Of the 135 patients who received the treatment as second-line therapy, 94 were disease-free during follow-up; 22 of 49 patients who received treatment as third-line or later therapy were disease-free. Of 40 patients with cancer that was refractory to standard-dose platinum, 18 were disease-free. A total of 98 of 144 patients who had platinum-sensitive disease were disease-free, and 26 of 35 patients with seminoma and 90 of 149 patients with nonseminomatous germ-cell tumors were disease-free. Among the 184 patients, there were three drug-related deaths during therapy. Acute leukemia developed in three additional patients after therapy. CONCLUSIONS Testicular tumors are potentially curable by means of high-dose chemotherapy plus hematopoietic stem-cell rescue, even when this regimen is used as third-line or later therapy or in patients with platinum-refractory disease.

A phase III study adding aprepitant to a 5HT3 receptor antagonist (5HT3-RA) plus dexamethasone in germ cell tumor (GCT) patients treated with 5-day cisplatin combination chemotherapy demonstrated a significant improvement in complete response (CR) (J Clin Onc 30:3998-4003, 2012). Fosaprepitant has demonstrated non-inferiority compared to aprepitant in single-day cisplatin chemotherapy and is approved as a single-dose alternative. This single-arm phase II study is the first clinical trial evaluating fosaprepitant in patients receiving multi-day cisplatin regimen. GCT patients receiving a 5-day cisplatin combination chemotherapy were enrolled. Fosaprepitant 150 mg was given IV on days 3 and 5. A 5HT3-RA days 1–5 (days 1, 3, and 5, if palonosetron) plus dexamethasone 20 mg days 1 and 2 and 4 mg po bid days 6, 7, and 8 was administered. Rescue antiemetics were allowed. The primary objective was to determine the CR rate—no emetic episodes or use of rescue medications. Accrual of 64 patients was planned with expected CR > 27 %. Sixty-five patients were enrolled of whom 54 were eligible for analysis. Median age was 33. Fifty-one patients received bleomycin, etoposide, and cisplatin (BEP) chemotherapy. CR was observed in 13 (24.1 %) patients (95 % Agresti-Coull binomial C.I. 14.5 %, 37.1 %). The data in this phase II study, in contrast to our prior phase III study, appears to indicate a lower CR rate with the substitution of fosaprepitant for aprepitant. It is unknown whether the substitution of fosaprepitant for aprepitant provides the same benefit in multi-day cisplatin that was achieved with single-day cisplatin. Trial registration Clinical trial information NCT01736917

Germ cell tumor patients progressing after high-dose chemotherapy (HDCT) have a dismal prognosis. A prior retrospective study of paclitaxel and gemcitabine enrolled 32 patients. All failed first-line chemotherapy and salvage therapy with HDCT. We now present long-term results.Eligible patients received BEP or similar first-line chemotherapy and subsequent HDCT. They were treated with paclitaxel (100 mg/m) on days 1, 8, and 15 and gemcitabine (1000 mg/m) on days 1, 8, and 15 every 4 weeks for a maximum of 6 cycles.Ten of 32 (31%) had an objective response (4 partial remissions and 6 complete responses). Four patients (12.5% of total) have enjoyed long-term survival; 3 are continuously disease free for 64, 94, and 122 months. None of these 3 received subsequent chemotherapy or surgery. A fourth patient relapsed after 72 months, and has now reachieved remission for 36+ months after treatment with the same regimen. These patients had 2, 2, 2, and 4 prior therapies, respectively, and a rising serum human chorionic gonadotropin (69 and 138 mIU/mL), α-fetoprotein (525 ng/mL), or increasing intrathoracic metastases. Longest prior response ranged from 5 to 24 months.Paclitaxel and gemcitabine salvage chemotherapy can offer long-term survival and probable cure in relapsed/refractory germ cell tumor patients after HDCT. This is an appropriate regimen in a taxane-naive and gemcitabine-naive patient population. This is the first example of a nonplatinum curative chemotherapy regimen in patients progressing after HDCT.

Purpose Initial cisplatin (CIS) combination chemotherapy will cure 70% of patients with disseminated testicular cancer. This phase II clinical trial evaluated the combination of CIS plus epirubicin (CIS-EPI) in patients with metastatic germ cell tumors (GCT) not amenable to cure with standard salvage therapy. Patients and Methods Between March 2001 and August 2005, 30 patients with GCT, who had received at least one previous CIS-based regimen, were enrolled. All patients were males, with median age 36 (range, 24 to 45 years). Twenty-one patients (70%) had experienced late relapses (> 2 years). Patients received EPI 90 mg/m2 on day 1 and CIS 20 mg/m2 on days 1 to 5 every 3 weeks for maximum of four cycles. Results Nineteen (63%) of 30 patients received all four cycles. Toxicity was primarily hematologic: grade 3/4 neutropenia, four patients (one neutropenic fever); two patients had grade 3 thrombocytopenia, and five patients had grade 3/4 anemia. Nonhematologic toxicity was grade 3 acute renal failure in two patients; grade 3 electrolyte wasting in two patients; grade 3 nausea/vomiting in eight patients; grade 3 elevation of aminotransferases in one patient; and grade 3 diarrhea in one patient. There were no occurrences of severe mucositis, cardiotoxicity, or treatment-related deaths. Nine patients achieved a complete remission; seven of these patients remain without evidence of disease at 25+, 27+, 29+, 44+, 45+, 46+, and 48+ months. One patient remains alive with stable pulmonary nodules at 28+ months. Conclusion CIS-EPI is an active regimen in metastatic GCT, with an acceptable toxicity profile. This regimen offers potential for long-term disease-free survival in this population.

Salvage therapy with high-dose chemotherapy (HDCT) and bone marrow transplant (BMT) or peripheral blood stem cell transplant (PBSCT) has curative potential in patients with recurrent germ cell tumor. However, patients with primary mediastinal nonseminomatous germ cell tumors (PMNSGCTs) have had poor results with any form of salvage chemotherapy including HDCT. We switched from BMT to PBSCT in 1996. One hundred sixteen of 184 patients (63%) with recurrent or refractory germ cell tumors treated from 1996 to 2004 were alive and continuously disease-free. PMNSGCTs were excluded from that study because of poor results in the patient population with HDCT and BMTs. In 2006, we resumed treating patients with recurrent PMNSGCT with 2 consecutive courses of HDCT consisting of carboplatin 700 mg/m2 × 3 plus etoposide 750 mg/m2 × 3 and each followed by an infusion of autologous peripheral-blood hematopoietic stem cells with a second course 3 to 4 weeks later. Twelve patients were treated: 11 as initial salvage chemotherapy and 1 as fourth-line therapy. Eight of the 12 patients had major thoracic resections at the time of the relapse after initial chemotherapy. Three of the 12 patients achieved complete remission (CR; 10, 15, and 50 months' duration). One patient remains continuously with no evidence of disease (NED) at 50 months. An additional patient is currently NED at 52 months with HDCT and subsequent surgery. Median survival for the 12 patients was 11 months (range, 4-52 months). Results with tandem transplant for recurrent PMNSGCT remain poor compared to primary testis cancer, but durable CR and probable cure can be achieved in a small subset of patients with PMNSGCT. In our opinion, salvage surgical resection if anatomically feasible is the preferred option for patients with PMNSGT progressing after initial chemotherapy.

Testicular cancer is the most common carcinoma in 20- to 40-year-old men. Eighty percent of patients with metastases achieve disease-free status with chemotherapy with or without surgical resection. Standard first-line chemotherapy is bleomycin, etoposide, and cisplatin (BEP) for three to four courses or etoposide and cisplatin (EP) for four courses. Forty percent of patients receiving chemotherapy will have permanently reduced sperm counts impairing future fertility. Sperm banking is an effective method of maintaining fertility. This retrospective study was performed to assess utilization and results from sperm banking, as well as the barriers to its use. Patients 18 and older who had received chemotherapy were given a five-item questionnaire on follow-up visit. This questionnaire included a mix of quantitative and qualitative questions. Two hundred patients enrolled in the study, and all 200 completed the questionnaire. Of the two hundred, 139 (70 %) patients chose not to bank sperm; 71 (51 %) of those were not interested, 25 (18 %) declined due to desire to start chemotherapy, 24 (17 %) were not offered, 12 (9 %) declined due to cost, and 7 (5 %) answered “other.” The average age at cancer diagnosis of patients who banked sperm was 28.4 as opposed to 32.6 for patients who did not (p = 0.003). The percentage of patients that had children before their diagnosis was 21 % in the sperm banking group, and 50 % in the group that did not (p = 0.0002). Sixty-one (30 %) chose to bank sperm; 11 of 61 patients (18 %) utilized the banked sperm; 9 of 11 (82 %) patients that utilized were successful; and 3 of 9 (33 %) successes resulted in multiple gestations. Sperm banking provides the opportunity for paternity in testicular cancer patients with reduced sperm counts following treatment. However, the majority of these patients chose not to bank sperm or were not offered the opportunity. A range of factors such as time, emotional state, patient age, disease stage, prior children, institutional practices, and cost all influence whether banking is offered to patients and taken up. The authors provide recommendations to help clinicians overcome some of these barriers.

Purpose: To retrospectively analyze the frequency and outcome of hCG and AFP rise at start of or within 1 week after initiation of second course of high-dose carboplatin and etoposide chemotherapy (HDCE) in patients with relapsed or refractory germ cell cancer. Patients and methods: A single-institution review of 391 patients treated with HDCE and peripheral blood stem cell rescue from Feb 1996 to December 2010 was performed. Each patient received 2 consecutive courses of 700 mg of carboplatin per square meter of body-surface-area (BSA) and 750 mg of etoposide per square meter of BSA, each for 3 consecutive days, and each followed by autologous stem cell infusion. The second HDCE was administered 3-4 weeks after the first course. Weekly tumor markers were obtained. Results: 25 of 391 (6.4%) patients were noted to have rising hCG, AFP or both at initiation or within 1 week of second course of HDCE. Fourteen patients had hCG rise (median 48.7 mIU/mL; range 3.2 – 8.863) and 11 AFP rise (median 18.3 ng/mL; range 4.2 - 1,018.8). Twenty-four of 25 patients had a subsequent decline in tumor marker with second course HDCE. Seven of 25 (28%) patients are continuously disease-free at median followup of 69 months (range 28-124 months). Conclusion: Tumor marker rise during second course of HDCE is uncommon. Although it represents an adverse prognostic variable, cure is still possible with institution of second course of HDCE.

4505Background: Patients (pts) with mGCT who relapse after initial chemotherapy (CT) can still be cured with second-line and even third-line regimens. We previously reported series of 184 pts treat...

Purpose: To evaluate rates of complete remission and overall survival for patients with relapsed pure seminoma treated with high-dose carboplatin and etoposide followed by peripheral blood stem cell transplant. Patients and Methods: Forty-eight consecutive patients with relapsed pure seminoma who were treated with high-dose chemotherapy (HDCT) and autologous peripheral blood stem cell transplant between May 1996 and June 2006 were retrospectively reviewed. Upon relapse (first, second, or third relapse) patients were given HDCT with carboplatin 700 mg/m2 and etoposide 750 mg/m2 for 3 consecutive days followed by infusion of peripheral blood stem cells. Here, we review both response and survival. Results: Thirty-eight (79%) of 48 patients obtained a complete response (CR) with overall survival of 75%. Median follow-up of all patients was 45.6 months. Twenty-two (92%) of 24 patients in first relapse achieved CR and are still alive and continuously disease-free. Sixteen (67%) of 24 patients had HDCT as third- or fourth-line therapy with 67% CR and overall survival of 64%. There were 3 treatment-related deaths, all of which occurred as third- or fourth-line therapy. Conclusion: HDCT results in high rates of both CR and overall survival in patients with first or later relapsed pure seminoma germ cell tumors.

Background The emergence of a primitive neuroectodermal tumor (PNET) within a germ-cell tumor (GCT) is rare. We assess the prognosis and response to treatment. Patients and methods Eighty-one patients were identified. Selected patients were treated with cyclophosphamide 1200 mg/m2, doxorubicin 75 mg/m2, and vincristine 2 mg i.v. alternating with ifosfamide 1.8 g/m2 × 5 days plus etoposide 100 mg/m2 × 5 days (CAV/IE). Ewing's sarcoma (EWS) translocation was assessed using a FISH-based method. Results Median follow-up was 41 months. Seventy-six patients had PNET in the primary tumor or in initial metastasis. Five harbored PNET only at relapse. Twenty-six of 76 underwent primary retroperitoneal lymph node dissection, 13 of whom had retroperitoneal PNET and four are dead of disease (DOD). Fifty of 76 were initially treated with GCT chemotherapy (n = 49) or CAV/IE (n = 1). Twenty-seven of these 50 underwent complete postchemotherapy resection of residual PNET and 17 are DOD. Ten patients received CAV/IE. Eight achieved an objective response, and five are currently alive. One of the 14 specimens examined carried the EWS translocation. Conclusions PNET of GCT origin is associated with an adverse outcome. For low-volume disease, surgery is the optimal initial therapy. CAV/IE may have a role in patients with unresectable disease.

This position paper, written on behalf of the MASCC Psychosocial Study Group, reviews the most common psychosocial concerns and needs of cancer patients during all phases of the cancer continuum, from diagnosis to death or survivorship. Developments in psychosocial care at both individual and systems levels are surveyed and summarized, along with gaps in knowledge and research and needed improvements in the dissemination and application of acquired knowledge and expertise. The roles of culture, spirituality, and religion as part of psychosocial care are reviewed, along with families’ and caregivers’ specific psychosocial concerns and needs, and areas of needed psychosocial interventions in supportive cancer care. Deficits in recognizing and meeting patients’ psychosocial needs at the system level are examined, and international guidelines and models of psychosocial care are reviewed, including their potential applications to local contexts. The paper calls for a shift to a new paradigm of care through adoption of an integrated approach to identify and meet the psychosocial needs of cancer patients and survivors as part of supportive care worldwide.

122 Background: Testicular cancer is the most common carcinoma in men ages 18-35. Eighty percent of patients with metastatic disease will be cured with cisplatin based chemotherapy. However, approximately 40% of patients receiving chemotherapy will have permanent azospermia or oligospermia, impairing future fertility. Sperm banking prior to chemotherapy is an effective method of maintaining fertility. This retrospective study was performed to assess utilization and results from sperm banking, as well as the barriers to its use. Methods: Patients 18 and older who were 1-year post chemotherapy were given a 5-item questionnaire on follow-up visit. The questionnaire included a mix of quantitative and qualitative questions. Results: 200 patients with metastatic testicular cancer including patients who started initial chemotherapy at other institutions, enrolled in the study and all completed the questionnaire. 139/200 (70%) chose not to bank sperm: 71 (51%) of those were not interested, 25 (18%) declined due to desire to start immediate chemotherapy, 24 (17%) were not offered, 6% of those not offered were from Indiana University, 12 (9%) declined due to cost, and 7 (5%) answered "other". The average age at cancer diagnosis of patients who banked sperm was 28.4 as opposed to 32.6 for patients who did not bank sperm (p = 0.003). The percentage of patients who had children before their diagnosis was 21% in the sperm banking group and 50% in the group that did not (p = 0.0002). Sixty-one (30%) chose to bank sperm, 11 of 61 patients (18%) utilized the banked sperm. 9 of 11 (82%) that utilized the banked sperm resulted in successful paternity: 3 of 9 (33%) produced twins. There were no birth defects. Conclusions: Sperm banking provides the opportunity for paternity in testicular cancer patients. However, the majority of these patients chose not to bank sperm or was not offered the opportunity. A range of factors such as time, emotional state, patient age, disease stage, prior children, institutional practices, and cost all influence whether sperm banking is offered and taken up. Physicians and patients need to be aware of the potential benefit of sperm banking.

135 Background: Survivors of germ cell tumors (GCT) may face long-term health risks We have previously reported the high incidence of hypogonadism (HG) in survivors of GCT. These patients also may be at risk for other chronic health and psychosocial problems. Methods: Patients treated with chemotherapy (Group 1) or with orchiectomy and/or other surgery or radiotherapy for GCT (Group 2), were 18-50 yrs of age, and not receiving supplemental testosterone at baseline were eligible. Total testosterone was measured at baseline. For patients receiving supplemental testosterone while on study, total testosterone was also measured at 3 and 6 months. Cancer diagnosis and treatment variables were obtained from medical records. Patients completed a validated quality of life (QOL) questionnaire at baseline, 3, and 6 mos. Measures included the Aging Males’ Symptoms (AMS) scale and NIH Patient Reported Outcome Management Information Systems (PROMIS) measures. Results: The rate of HG ( < 300 testosterone) at baseline did not differ between Group 1 and Group 2 (p = 0.45). Compared to non-HG, patients with HG measured at baseline were significantly more likely to have a BMI in the obese ( > 30; 57% vs 19%) range (p < 0.001). Improvements in testosterone during treatment from baseline to follow-up were strongly correlated with improvements in AMS (r = 0.51, p = 0.001) and moderately correlated with improvements in general health (r = 0.32, p = .049). Multivariable models using baseline variables demonstrated that baseline HG was significantly associated with worse baseline quality of life in the areas of general health, sleep quality, and fatigue. BMI in the obesity range was significantly associated with worse general health. Conclusions: Patients who were treated for GCT are at higher risk of HG. This subsequently increases the risk of having a BMI in the obese range, which in turn is associated with worse QOL. Treating HG is associated with improvements in AMS scale.

Purpose To determine long-term survival and potential cure with salvage chemotherapy with paclitaxel plus gemcitabine after progression after both cisplatin combination chemotherapy and subsequent high-dose chemotherapy with tandem transplantation. Patients and Methods One hundred eighty-four patients received salvage high-dose chemotherapy at Indiana University (Indianapolis, IN) from February 1996 to December 2004. After further evidence of progressive disease, 32 patients were subsequently treated with paclitaxel 100 mg/n2 over 1 hour plus gemcitabine 1,000 mg/m2 over 30 minutes, days 1, 8, and 15 every 4 weeks for a maximum of six courses. This is a retrospective review of this patient population. Patients were evaluated for response, duration of response, and survival. Patients were ineligible if they received prior paclitaxel or gemcitabine. Results Ten (31%) of 32 patients achieved objective response, including four partial remissions (2- to 6-month duration) and six complete responses (CRs). Four of these six CRs (12.5% of total patient population) are continuously disease free (NED) with paclitaxel plus gemcitabine alone (no postchemotherapy surgery) at more than 20, 40, 44, and 57 months from start of paclitaxel plus gemcitabine, respectively. One additional CR is currently NED more than 63 months after paclitaxel plus gemcitabine with two subsequent resections of carcinoma. Conclusion Long-term disease-free survival is possible with paclitaxel plus gemcitabine in this patient population that progressed after high-dose chemotherapy, and had not received prior paclitaxel or gemcitabine.

e20737 Background: In our prior phase III study (J ClinOnc 30:3998-4003, 2012) the addition of aprepitant to 5-day cisplatin regimens for germ cell tumors showed a significant improvement in comple...

e17574 Background: Testicular cancer is the most common malignancy in 15-35 year old men. It is also highly curable with over 95% five-year survival rates. However, forty percent of patients receiv...

9576 Background: The vast majority of men with germ cell tumors (GCT) will be cured of their disease and may face long-term risks associated with survivorship. This may include hypogonadism (HG), w...

391 Background: The remarkable success of cisplatin-based chemotherapy in curing metastatic TC has been accompanied by potential life-threatening sequelae, including CVD. Most prior studies, however, have been conducted in Europe and included older chemotherapy regimens. We examined CVD risk factors in an ongoing multi-center clinical study of TCS given modern cisplatin-based chemotherapy (CHEM) at centers in North America (NCI 1R01 CA157823-02). Methods: TCS aged ≤49 years at time of first-line CHEM were eligible to undergo clinical examination and complete a questionnaire regarding co-morbidities, lifestyle behaviors, and prescription drug use. Results: We evaluated the first 443 consecutively enrolled TCS (23% seminoma; 77% nonseminoma) with most having stage II (52%) or III (28%) disease. The median age at time of TC diagnosis was 32 years (range 15-49 years) and median time since completion of chemotherapy was 59 months (range 1-24 years). Patients were largely white (90%), married (62%), and had full-time employment (82%) and health insurance (88%). 8% of TCS were current smokers. 48% of TCS had gained >10 lbs after CHEM with 29% having a ≥102 cm (40 inch) waist circumference, and 43% and 31% having a body mass index of 25 to 2 (obese), respectively. A sizable proportion of men had abnormal systolic (21% with 130-139 mm Hg and 17% with ≥140 mm Hg) and diastolic (35% with 80-89 mm Hg and 13% with ≥90 mm Hg) blood pressure. 14%, 11%, and 5% TCS indicated that they currently used medications for hypertension, cholesterol and diabetes, respectively. Cardiac conditions were reported by 32 TCS (7%), including angina (N=2), angioplasty/stent placement (N=1), myocardial infarction (N=1), transient ischemic attack (N=1), stroke (N=2), peripheral vascular disease (N=12), deep vein thrombosis (N=23), and pulmonary embolism (N=15). Conclusions: A number ofCVD risk factors are present in a contemporary North American cohort of TCS after CHEM. Future analytic studies should focus on mechanistic investigations to facilitate the development of screening and preventive efforts for CVD in high-risk patients.

The aims of this study were to assess the safety and antiemetic efficacy of multiple-day dosing of palonosetron plus dexamethasone in patients receiving highly emetogenic multiple-day cisplatin-based chemotherapy for germ cell tumors.Forty-one men undergoing 5-day cisplatin-based chemotherapy for testicular cancer received palonosetron 0.25 mg IV once daily 30 min before chemotherapy on days 1, 3, and 5 plus IV dexamethasone 20 mg before chemotherapy on days 1 and 2, and 8 mg PO bid on days 6 and 7 and 4 mg bid on day 8. Safety and efficacy were assessed in 24-h intervals for 9 days. Efficacy endpoints included emesis, intensity of nausea and its interference with patient functioning, and rescue antiemetic use. A subset of patients (n = 11) was studied for electrocardiograph effects and pharmacokinetic evaluation.This multiple-day antiemetic regimen was safe, with headache and constipation the most common treatment-related adverse events, mostly mild. Neither adverse events nor electrocardiographic changes appeared to increase in frequency, duration, or intensity over time despite a 1.42-fold systemic accumulation of palonosetron with repeated doses. The majority of patients had no emesis at any time throughout days 1-5 (51%) or days 6-9 (83%), had no moderate-to-severe nausea, and did not require rescue medication. Most patients reported that nausea had no significant effect on daily functioning on days 1-4 (72%) and days 5-9 (85%).Palonosetron on days 1, 3, and 5, along with a regimen of dexamethasone, was safe and well tolerated and effectively controlled both nausea and emesis in patients undergoing 5-day cisplatin-based chemotherapy for testicular cancer.

Chemotherapeutic agents are classified by their degree of emetogenicity. Highly and moderately emetogenic agents require antiemetic prophylaxis for chemotherapy-induced nausea and vomiting. Intravenous etoposide is listed as having low emetic potential. However, oral etoposide is categorized as having moderate emetogenicity. Daily oral etoposide is used in refractory germ cell cancer patients. We prospectively evaluated the emetic potential of oral etoposide in this patient population.Between August 2003 and February 2006, 16 patients with refractory germ cell cancer received single-agent, daily oral etoposide 50 mg/M(2) for 21 consecutive days every 4 weeks. All patients had progressed after cisplatin combination chemotherapy and had received high-dose chemotherapy with carboplatin plus etoposide (intravenously) with peripheral blood stem cell transplant. No patient received prophylactic antiemetics. Patients completed a six-question Multinational Association of Supportive Care in Cancer (MASCC) antiemetic tool during each day of etoposide during the first 21-day course. Nausea intensity and duration were recorded. Number of emetic episodes and any antiemetic medications were recorded.All 16 patients completed the six-question MASCC form. Eleven of 16 had no nausea or vomiting and two other patients had only minimal nausea, despite absence of any prophylactic antiemetics. Only two patients required antiemetic support. Two patients experienced emesis for a single episode. One patient had nausea on days 9-20 with a MASCC rating of 3-6, and one patient had continued mild nausea (MASCC rating 1-3) for all 21 days.Daily oral etoposide has a low probability of producing chemotherapy-induced nausea and/or vomiting and, in our opinion, does not require prophylactic antiemetics.

Purpose: To determine whether fluoxetine improves overall quality of life (QOL) in advanced cancer patients with symptoms of depression revealed by a simple survey. Patients and Methods: One hundred sixty-three patients with an advanced solid tumor and expected survival between 3 and 24 months were randomly assigned in a double-blinded fashion to receive either fluoxetine (20 mg daily) or placebo for 12 weeks. Patients were screened for at least minimal depressive symptoms and assessed every 3 to 6 weeks for QOL and depression. Patients with recent exposure to antidepressants were excluded. Results: The groups were comparable at baseline in terms of age, sex, disease distribution, performance status, and level of depressive symptoms. One hundred twenty-nine patients (79%) completed at least one follow-up assessment. Analysis using generalized estimating equation modeling revealed that patients treated with fluoxetine exhibited a significant improvement in QOL as shown by the Functional Assessment of Cancer Therapy–General, compared with patients given placebo (P = .01). Specifically, the level of depressive symptoms expressed was lower in patients treated with fluoxetine (P = .0005), and the subgroup of patients showing higher levels of depressive symptoms on the two-question screening survey were the most likely to benefit from treatment. Conclusion: In this mix of patients with advanced cancer who had symptoms of depression as determined by a two-question bedside survey, use of fluoxetine was well tolerated, overall QOL was improved, and depressive symptoms were reduced.

TPS9658 Background: Germ cell tumors (GCTs) represent a model for a curable malignancy. Most treated patients will live active lives. Patients treated with platinum combination chemotherapy may be ...

TPS4594 Background: Germ cell tumors (GCT) account for 1% of malignancies of American males. Cisplatin combination chemotherapy is the cornerstone for curative therapy in metastatic GCT. Cisplatin ...

Objective: This phase II study was conducted to determine the activity of imatinib (gleevec) in heavily pretreated patients with KIT-positive metastatic germ cell tumor. Materials and Methods: From June 2002 through April 2005, 18 patients with refractory germ cell tumors were tested for KIT expression by immunohistochemistry. All patients screened were deemed to be incurable with further standard chemotherapy or surgery. Six patients were eligible and treated with imatinib 600 mg/d orally. Results: There were no complete or partial remissions. Five of 6 patients had progressive disease and 1 patient had stable disease with a >50% decline in serum alpha-fetoprotein for 3 months before developing further progression. Conclusion: In this small sample size, there was no evidence of significant antitumor activity of imatinib in patients with KIT-positive refractory germ cell tumors.

e15621 Background: Thromboembolism (TE) accounts for significant morbidity and mortality in cancer patients. Rates of TE have been reported from 0.9%-28.0%, depending on the population. Patients with germ cell tumors have a 4.0-8.4% risk of TE following platin chemotherapy. Our patients are high-risk, many with advanced disease receiving high-dose chemotherapy and peripheral blood stem cell rescue. We sought to more completely understand TE events in advanced germ cell tumor patients. Methods: Forty-four consecutive patients visiting our germ cell tumor clinic between 11/05/2012 and 1/22/2013 were selected. Data were collected by retrospective chart review from tumor diagnosis until TE (ranging from TE on diagnosis to 20 years later). A logistic regression model was fitted to determine variables that predispose patients to TE. Results: In our patient series, seven (15.9%) had venous TE and none had arterial events. Five patients (11.4%) had TE within 16 weeks of chemotherapy, and 2 at 10 and 19 years after diagnosis, respectively. Two had bilateral pulmonary emboli (PE) (4.5%), 3 had upper or lower extremity DVTs, or both, and 1 had bilateral PE and DVTs. Five patients with TE had nonseminomatous tumors, 2 had non-testis primaries, 4 had relapsed disease, 2 with late relapse (>7 years), 6 had metastatic disease, 3 had retroperitoneal lymph node dissection, and all 7 received platin chemotherapy. In logistic regression analysis, significant risk factors for TE included relapse (P= .016), bulky retroperitoneal lymphadenopathy (P= .006), alpha-fetoprotein >10,000 (P= .047) beta-HCG > 1,000 (P= .020), chemotherapy (P= .031), platin-refractory disease (P= .055), and poor risk disease compared to good risk disease (P=.020). Conclusions: Germ cell tumor patients have a high risk of venous TE. Those with relapsed disease, bulky retroperitoneal lymphadenopathy, platin chemotherapy, platin-refractory, or poor risk disease are at increased risk. Our estimates are higher than previously reported and in contrast to earlier studies, do not include arterial TE. To confirm our findings, we will extend this study to 100 patients. If confirmed, this pattern of TE events may be a consequence of advanced stage disease in our patients.

4534 Background: Based on the International Germ Cell Cancer Collaborative Group (IGCCCG), IRGCT represents 26% of non-seminomas and 10% of seminomas with 2 year PFS of 74% (63-85%). Most patients are treated with 4 cycles of Bleomycin, Etoposide and Cisplatin (BEP). However, the optimal therapy for this heterogeneous group is not well defined. Our hypothesis was that many patients with IRGCT may not require BEPx4 as they are clinically closer to good risk rather than to poor risk disease. Methods: We conducted a retrospective analysis of all patients with testicular cancer seen at Indiana University (IU) between 2000- 2010. We identified 170 pts with IRGCT of whom 84 consecutive pts received their therapy at IU. 2 chemotherapy categories were identified: BEP (or equivalent) x4 or BEPx3 (+/-EPx1). Results: 45 pts received either BEPx4 (41), VIPx4 (2) or BEPx2 followed by HDCTx2 (2). 39 pts received BEPx3 (9) or BEPx3+EPx1 (30). Treatment decisions were based on clinical characteristics and markers amplitude. There were 78 (93%) non-seminoma, 6 (7%) seminoma. 27 (32%) stage II and 57 (68%) stage III. Mean AFP 3899 (range 1000-9550; n=50), mean hCG 16354 (range 5000-49000; n=34). The overall 1 and 2 year Kaplan-Meier estimates were 93% and 87% for PFS and 98% and 92% for OS. Results are depicted below. Conclusions: Our results for patients with IRGCT treated from 2000-2010 are superior to the IGCCCG pts treated from 1975-1990. Routine administration of BEPx4 probably represents overtreatment in a substantial percent of IRGCT. [Table: see text]

4598 Background: Metastatic germ cell cancers are highly chemosensitive and have 80% cure rate with cisplatin based chemotherapy. Post-chemotherapy teratoma can usually be surgically resected. However, teratoma, which is pleuripotent tissue, can undergo malignant transformation along mesodermal elements to PNET. Unlike teratoma, PNET can metastasize and render a patient unresectable and incurable. We report the results of treatment of patients with PNET with cyclophosphamide + doxorubicin + vincristine (CAV) alternating with ifosfamide + etoposide (IE). Methods: We reviewed 81 patients with histologically confirmed PNET transformed from testicular teratoma at Indiana University from 1998 to 2011. We identified 13 cases who were treated with chemotherapy comprising cyclophosphamide 1000-1200 mg/m2, doxorubicin 50-75 mg/m2, and vincristine 2 mg alternating with ifosfamide 1.8 grams/m2 plus etoposide 100 mg/m2 for 5 days. Treatment was given every 3 weeks with a maximum of 6 cycles or until progression or undue toxicity. Hematopoeitic growth factors were usually incorporated. The remaining 68 patients underwent surgical resection. Results: Ten patients had unresectable disease and 3 were treated in an adjuvant setting. Median age was 31 years (range 20-53). Ten of 13 patients had received prior platinum based chemotherapy. Eight of 10 evaluable patients achieved objective response. Five of those were rendered with no evidence of disease(NED) with further surgery. Although 4 of the 5 patients subsequently relapsed, 1 patient remains alive with NED at 69 months. The 3 patients who received adjuvant treatment after retroperitoneal lymph node dissection (RPLND) are alive with NED at 1, 4 and 8 years. Conclusions: CAV and IE alternating chemotherapy has high objective response rate for PNET transformed from teratoma and results in occasional long term disease free survival when combined with subsequent resection. We recommend adjuvant CAV alternating with IE chemotherapy for patients with PNET after RPLND due to the high probability of recurrent disease and their high chemosensitivity to this regimen.

4562 Background: Germ cell tumor (GCT) patients progressing after high-dose chemotherapy (HDCT) have a dismal prognosis. A prior phase II trial of paclitaxel and gemcitabine enrolled 32 patients. All failed first-line chemotherapy and HDCT (J Clin Oncol 25; 513, 2007). We now present long-term results. Methods: Eligible patients received BEP or similar first-line chemotherapy and HDCT. They were treated with paclitaxel 100mg/m2 and gemcitabine 1,000mg/m2 on days 1, 8, and 15 every 4 weeks for a maximum of 6 cycles. Results: Ten of 32 (31%) had an objective response (4 partial remissions and 6 complete responses). Four patients (12.5% of total) are continuously disease free (NED) for 64, 94, 96, and 103 months. None of these four received subsequent chemotherapy or surgery. They had three, three, three, and five prior therapies, respectively. Longest prior response was five to 24 months. All relapsed with a rising hCG (69 to 138 mU/mL) or AFP (525 to 2000 ng/mL). Conclusions: Paclitaxel and gemcitabine sal...

4579 Background: Salvage chemotherapy with Ifosfamide based regimen or high dose chemotherapy (HDCT) has curative potential in GCTs. We still need novel therapies for patients where cure is not pos...

4612 Background: Metastatic germ cell tumors that cannot be successfully treated by platinum based initial chemotherapy regimen are potentially curable with salvage chemotherapy. Relapsed or refractory testicular cancer has been treated at Indiana University with two courses of high-dose carboplatin and etoposide chemotherapy (HDCE), each course followed by peripheral stem cell rescue. Einhorn et al published the result of 184 consecutive recurrent metastatic patients treated 1996-2004 with two cycles of HDCE. 63% of these 184 patients were continuously NED with median follow-up 48 months (NEJM 357,340 2007). Several patients were noted to have rising tumor markers—hCG and/AFP—during their second course of high-dose chemotherapy. Similar phenomenon has been noted in some patients treated subsequently. We present retrospective analysis of the frequency and outcome of a rising tumor marker at start of second course of HDCE or within 1 week after initiation of second course. Methods: 391 patients have been t...

e16121 Background: Metastatic testis cancer is uniquely chemosensitive and highly curable. Residual teratoma can be surgically resected. However, testicular teratoma can differentiate along endodermal, ectodermal, or mesodermal elements (malignant transformation of teratoma), with capacity to metastasize and not be amenable to surgical resection. We report results of malignant transformation of teratoma to metastatic PNET treated with PNET based chemotherapy. Methods: Retrospective review of 42 patients with PNET in testis or at metastatic sites seen at Indiana University from 1999–2007. Of these 42 patients, 10 had inoperable or unresectable PNET treated with cyclophosphamide 1200 mg/M2, doxorubicin 75 mg/M2, and vincristine 2 mg IV alternating with ifosfamide 1.8 grams/M2 × 5 days plus etoposide 100 mg/M2 × 5 days. Courses were given every 3 weeks for 6 courses or until progression or undue toxicity. Results: 9 of 10 patients had at least 1 prior platinum based combination chemotherapy regimen for their germ cell tumor. Tumor markers (human chorionic gonadotropin and alphafetoprotein) were normal at start of chemotherapy for biopsy proven PNET. Eight of 10 achieved objective response. Two of 10 are currently disease-free for 16 and 33 months from initiation of PNET specific chemotherapy and 3 other patients are alive with disease at 73, 34, and 30 months. These 5 patients all had subsequent surgery. Conclusions: PNET specific chemotherapy has a high objective response rate for malignant transformation of teratoma to PNET, with some patients capable of long-term survival with chemotherapy followed by surgical resection. [Table: see text]

5029 Background: There is controversy concerning management of patients (pts) with nonseminomatous germ cell tumor (NSGCT) who obtain a chemotherapy-induced complete radiographic (2 years (range 3–13 years). All 5 are currently disease free. Six pts recurred in the RP and 2 are DOD. Six pts recurred outside the RP. Two of these 6 are DOD. Conclusions: Pts obtaining CR after primary chemotherapy can be safely observed without RPLND. Relapses are rare and potentially curable with further treatment. No significant financial relationships to disclose.

5081 Background: Malignant transformation of teratoma to PNET is a rare entity. Surgical resection has been the mainstay of therapy because these tumors are not curable with cisplatin based chemotherapy. We report long-term survival and potential cure with retroperitoneal lymph node dissection (RPLND) and PNET specific chemotherapy. Methods: Retrospective review of 75 patients (pts) with PNET in the testis or at distant metastasis treated from Jan 1988 to Dec 2007. 74 had RPLND as part of initial treatment or at relapse. PNET specific chemotherapy consisted of cyclophosphamide, doxorubicin, vincristine alternating with ifosfamide and etoposide. Available PNET specimens were tested for the Ewing's sarcoma (EWS) translocation using a FISH-based method. Results: The median follow-up was 40 months (range 2 to 235). 27 pts presented with clinical stage I disease. 18 underwent primary RPLND with PNET in the retroperitoneum in 5. 4 are dead of disease (DOD). 9 elected surveillance or adjuvant chemotherapy. 8 relapsed with PNET. 4 are DOD. 48 pts presented with metastatic disease. 20 are DOD, 24 have no evidence of disease (NED) and 4 are alive with disease. 50 of 75 pts had PNET documented metastasis with an estimated 5 years disease specific survival of 47%. 10 of these were treated with PNET specific chemotherapy for unresectable disease. 8 of the 10 achieved objective response with the duration of response ranging from 4 to 73 months. 2 pts are NED. 2 additional pts were treated with PNET specific chemotherapy as adjuvant to RPLND. Both are continuously NED. Specimens from 14 pts were tested for the EWS translocation, 2 were positive. Conclusions: Malignant transformation of teratoma to PNET carries an adverse prognosis. RPLND is an integral part of the therapeutic strategy. PNET specific chemotherapy, adjuvant to RPLND or for treatment of unresectable disease followed by surgery, may result in long-term survival and potential cure. No significant financial relationships to disclose.

8607 Background: Fractionated cisplatin is highly emetogenic; despite 5HT3 receptor antagonists + DEX, patients still experience acute and delayed CINV. PALO, a novel 5HT3 antagonist, is superior to conventional 5HT3 antagonists in protecting patients from emesis with a 0.25-mg IV dose prior to single-day CT. To assess the efficacy and safety of PALO in 40 patients with germ cell tumors receiving multiple-day cisplatin-based CT, a phase II multicenter study is being conducted. Methods: Adult men receiving 5-day cisplatin-based (20 mg/m2/d) CT received PALO 0.25 mg IV 30 min before CT on days 1, 3, and 5 and DEX 20 mg qd (po or IV 30 min before CT) on days 1–2; 8 mg po bid on days 6–7; and 4 mg po bid on day 8. Rescue medication was allowed at investigator discretion. Endpoints included emetic episodes (EE), nausea intensity, and rescue use, recorded in diaries for 9 consecutive 24-h periods. Interference with functioning due to nausea on a 4-point scale (none, a little bit, quite a bit, very much) was assessed with the validated Osoba nausea module on days 1, 5, and 10; safety was assessed at all follow-up encounters. Results: To date, 32 patients are evaluated, median age 35 years, 81% CT-naïve. Prior to CT, 97% of patients reported no more than a little interference with functioning from nausea. Most patients reported no significant interference with functioning due to nausea on days 1–4 of cisplatin (73% reported none/a little bit) and days 5–9 (87% none/a little bit). PALO + DEX was well tolerated; treatment-related adverse events were mild-moderate headache (18.8%), constipation (6.3%), and abdominal pain (3.1%), none serious. Conclusions: Three doses of PALO + 5 doses of DEX over an 8-day period effectively prevented both emesis and significant nausea in the majority of patients with germ cell tumors receiving multiple-day cisplatin-based CT. This regimen appears to be an improvement over historical CINV control. [Table: see text] [Table: see text]

18618 Background: Chemotherapy agents are classified by their degree of emetogenicity. Agents with high or moderate emetogenicity are treated with a 5HT3 antagonist + dexamethasone to mitigate acute and delayed chemotherapy-induced nausea and vomiting. Intravenous etoposide (E) has low probability of nausea and/or vomiting. However, at the 2004 Perugia International Antiemetic Consensus meeting, oral E was listed as a moderately emetogenic drug (Supp Care Cancer 13:80–84, 2005). Daily oral E has been used to treat refractory germ cell cancer. We prospectively evaluated the emetic potential of daily oral etoposide in this patient (pt.) population. Methods: Between 8/03 and 12/05, 13 male pts. with refractory germ cell cancer were treated with single agent daily oral E 50 mg/M2 day × 21 days every 4 weeks. All had progressed following cisplatin combination chemotherapy and had previously received high dose chemotherapy with carboplatin + E (intraveneously) with peripheral blood stem cell transplant. Median age was 35 (range 14 to 54). No pt. received prophylactic antiemetics. Pts. completed a 6 question Multinational Association Supportive Care Cancer (MASCC) antiemetic tool each day they received E. Intensity and duration of nausea were recorded, with 0 being none and 10 being most severe. Additionally, pts. were asked if they experienced vomiting. The number of vomiting episodes as well as any antiemetic medications were recorded. Data on 25 pts. will be presented and we currently have information on 13 pts. Results: 13 pts. completed the MASCC form. Only 2 pts. required antiemetic support. 1 pt. experienced emesis × 1 on day 1 and 1 pt. experienced emesis × 1 on day 11. 1 pt. experienced nausea on days 9 through 20 with a MASCC rating of 3–6. 1 pt. documented nausea day 1 through 21 with a MASCC rating of 1–3. 2 pts. experienced a MASCC rating of 1 of their nausea, 1 pt. on day 1 and 1 pt. on day 2. Overall, 8 of 13 pts. had no nausea or vomiting despite the absence of any antiemetics and 2 other patients had only minimal nausea for a single day. Conclusions: Daily oral E has only a low probability of emesis and does not require prophylactic antiemetics. [Table: see text]

4588 Background: A previously published ECOG study of paclitaxel (P) plus gemcitabine (G) in refractory germ cell tumors achieved a 21% response rate (6 of 28 pts.) (JCO 20:1859, 2002). Two patients are continuously NED for 4+ years. Neither had prior HDCT. High dose salvage chemotherapy with carboplatin + etoposide and peripheral blood stem cell transplant has curative potential. Subsequent chemotherapy after progression following HDCT has only rarely achieved durable remission. We have retrospectively reviewed pts. treated at Indiana University with P + G after failure to cure with initial cisplatin combination chemotherapy and salvage HDCT (± other salvage regimens). Methods: 184 patients received salvage HDCT from February 1996 to December 2004. After further progression, 33 pts. were treated with P 100 mg/M2 over 1 hour and G 1000 mg/M2 over 30 minutes days 1, 8, and 15 every 4 weeks for a maximum of 6 courses. Pts. were ineligible if they received prior P or G. 26 pts. received P + G as 3rd line, 6 as 4th line and 1 as 5th line chemotherapy. Results: Toxicity was primarily myelosuppression and neuropathy, as previously described with P + G (JCO 20:1859, 2002). There was no treatment related mortality. 10 of 33 pts. achieved objective response including 4 partial (2 to 6 months duration) and 6 complete responses (C.R.). 4 of the 6 C.R.s are continuously NED with P + G alone at 14+, 34+, 44+, and 45+ months from start of P + G. One additional C.R. is currently NED 54+ months after P + G, with 2 subsequent resections of carcinoma. Conclusions: Long-term disease free survival and potential cure is possible with P + G in this patient population after progression following HDCT. [Table: see text]

Marijuana has been used for over 2 centuries. Its major psychoactive constituent, delta-9-tetrahydrocannabinol (THC) was isolated in 1964 and first used to control nausea and vomiting during chemotherapy in the 1970s. THC has cardiovascular, pulmonary and endocrinological effects as well as actions on the central nervous system. Alterations in mood, memory, motor coordination, cognitive ability, sensorium, spatial- and self-perception are commonly experienced. The precise antiemetic mechanism is unknown. THC and nabilone act at a number of sites within the central nervous system. Cannabinoids have also been shown to inhibit prostaglandin synthesis in vitro. In controlled clinical trials, THC is superior to placebo and prochlorperazine in antiemetic effectiveness. Effectiveness of THC correlates to a 'high' experienced by the patient. A variety of chemotherapy regimens respond to THC including high-dose methotrexate and the doxorubicin, cyclophosphamide, fluorouracil combination. Cisplatin is more resistant. Side effects are generally well tolerated but may limit THC use in the elderly or when high doses are administered. Nabilone, a synthetic cannabinoid, is also an effective antiemetic which is more active than prochlorperazine in preventing chemotherapy-induced emesis, including cisplatin-containing regimens. Side effects are similar to THC and may be dose-limiting. Levonantradol, another synthetic cannabinoid, is an effective antiemetic. It may provide more flexibility in the outpatient setting since it can be administered orally or intramuscularly. Most side effects are mild except for dysphoria which may be dose-limiting.