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The efficacy of nab-paclitaxel in patients with metastatic breast cancer (MBC) has been demonstrated in randomized clinical trials. However, real-world evidence on effectiveness remains limited. The primary objective of this multicenter prospective study was to assess the overall response rate (ORR) of patients with MBC treated with nab-paclitaxel. Secondary objectives included progression-free survival (PFS), overall survival (OS) and quality of life, assessed with the Functional Assessment of Cancer Therapy-Breast (FACT-B) instrument. Eligible patients (N = 150; 36% with de novo MBC presentation) with a median age of 64.5 years were enrolled (86% were ER+, 33.3% (50/150) were ≥ 70 years of age and 53% were treated in the third or later line of treatment). A median of 6 cycles were administered but 26% of patients required dose reduction due to toxicity. The ORR was 26.7% [95% confidence interval (CI) 19.6–33.7], the median PFS was 6.2 months (95% CI 5.2–7.3), and the median OS 21.1 months (95% CI 17.2-not estimable). There was no statistical significant difference in the median PFS of patients

Introduction: Nanoparticle albumin-bound (nab)-paclitaxel (nab-P) is approved for the treatment of patients with metastatic breast cancer (MBC) who have failed first-line treatment for metastatic disease and for whom standard, anthracycline containing therapy is not indicated. Real-world evidence on the effectiveness of nab-P is sparse. From this perspective, this non-interventional study was designed to assess the impact of nab-P on the clinical outcomes and the quality of life of patients with MBC in the routine care of Greece. Materials and methods: This multicenter prospective study enrolled consented females with MBC initiated (≤7 days prior to enrollment) on nab-P according to physicians decision. Clinicopathologic parameters and patient-reported outcomes [Functional Assessment of Cancer Therapy-Breast (FACT-B)] were collected at approximately 9-week intervals during the first 12 months of study participation and approximately every 18 weeks thereafter, until the end of the study observation period (maximum 30 months). Results: Between April 2016 and October 2017, 150 eligible patients (99.3% Caucasian) were enrolled in the study in 16 oncology centers. The patients’ median age was 64.5 years (range: 30.7-84.0) and ECOG performance status was 0 in 66.4% and 1 in 26.2%. 45.3% of patients had ≥1 comorbidity (21.3% cardiovascular diseases). The median time elapsed since MBC diagnosis was 22.4 months, while 36.0% of patients were de novo metastatic. The distribution of hormone receptor (HR)/human epidermal growth factor receptor 2 (HER2) status was 74.6% HR+/HER2-, 11.9% HR-/HER2-, 11.2% HR+/HER2+, and 2.2% HR-/HER2+. Most commonly occurring metastatic sites were the bones (55.3%), lung (50.0%), and liver (40.0%). Prior taxane-based therapy was annotated in 40.0% of patients. Of the patients, 11.3% received nab-P as first, 36.0% as second, 23.3% as third, and 29.3% as fourth or further treatment line. A median of 6 cycles (range: 1-33) was administered; 42.7% of the patients completed >6 and 22.0% >8 cycles. Dose reductions were required for 26.0% of the patients, mainly due to toxicity. The objective response rate was 26.7% and the clinical benefit rate was 44.0%. After a median follow-up of 19.3 months, 92 patients had progressed and 57 had died (14 without progression). The median progression-free survival (PFS) was 6.2 months [95% confidence interval (CI): 5.2-7.3]. The 6- and 12-month PFS rates were 50.6% and 30.5%, respectively. The median overall survival was 21.1 months (95% CI: 17.2-not estimable). Liver [hazard ratio (HR): 1.81; 95% CI: 1.24-2.66] and lung (HR: 1.53; 95% CI: 1.04-2.25) metastases were associated with a higher risk of progression or death. No statistically significant change in the patients’ baseline FACT-B total score (median: 93.0) was observed. The serious and non-serious adverse event (AE) incidence rates were 12.7% and 48.0%, respectively with a total of 37 grade ≥3 AEs (not including disease progression) reported. Conclusion: This study generated real-world evidence on the effectiveness of nab-paclitaxel; no new safety signals emerged. Citation Format: Anna Koumarianou, Paris Makrantonakis, Flora Zagouri, Christos Papadimitriou, Athina Christopoulou, Epaminontas Samantas, Christos Christodoulou, Amanda Psyrri, Dimitris Bafaloukos, Gerasimos Aravantinos, Pavlos Papakotoulas, Sofia Baka, Charalampos Andreadis, Athanasios Alexopoulos, Iliada Bombolaki, Katerina Kampoli, Sofia Liori, Kiki Karvounis, Alexandros Ardavanis. Real-world multicenter, prospective study of the effects of nab-paclitaxel on clinical outcomes and quality of life of patients with metastatic breast cancer in Greece. The ‘ABReast’ study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-15-07.

Background The International Duration Evaluation of Adjuvant Chemotherapy (IDEA) aimed to investigate whether a 3 months (3M) of oxaliplatin/fluoropyrimidine-based adjuvant chemotherapy (CT) is non-inferior to the 6-month (6M) administration in 3-year disease-free survival (3yDFS) in high-risk (HR) stage II or stage III colon cancer (CC). Methods Hellenic Oncology Research Group (HORG)-IDEA randomized patients between 3M and 6M of CT with FOLFOX4 or CAPOX. Results In total 1115 patients, 413 with HR stage II and 702 with stage III CC, were randomized. The median follow-up was 67.0 (38.3–126.0) months. Overall, 394 DFS events (202 in 3M arm and 192 in 6M arm) where recorded. The 3yDFS rate was 77.2% [95% confidence interval (CI) 72.1% to 82.3%] for 3M and 77.9% (72.6% to 82.5%) for 6M of treatment [hazard ratio (HR) 1.05 (95% CI 0.61–1.55); P=0.647]. Eighty DFS events (3M N=41; 6M N=39) were observed in HR stage II patients for a 3yDFS rate of 82.7% and 83.4%, respectively (HR 1.05; 95% CI 0.68–1.63, P=0.829). For stage III patients, 314 DFS events (3M N=161 and 6M N=153) were observed, for a 3yDFS rate of 72.9% for 3M versus 74.1% for 6M (HR 1.06; 95% CI 0.81–1.42, P=0.622). For HR stage II patients receiving FOLFOX4, 3yDFS rate was 76.7% for 3M and 79.3% for 6M (HR 1.21; 95% CI 0.54–2.70). For HR stage II patients receiving CAPOX the 3yDFS rate was 85.4% for 3M and 83.8% for 6M (HR 0.99; 95% CI 0.59–1.67). For stage III patients receiving FOLFOX4, the 3yDFS rate was 71.5% for 3M and 77.3% for 6M (HR 1.18; 95% CI 0.74–1.86). For stage III patients receiving CAPOX, the 3yDFS rate was 74.5% for 3M and 74.7% for 6M (HR 0.99; 95% CI 0.70–1.44). Conclusions The results of the HORG-IDEA study are in line with those of the global IDEA project, indicating that the 3yDFS is dependent on the administered adjuvant regimen and the choice and duration of regimen should be personalized. ClinicalTrials.gov Registration Number NCT01308086.

Although colorectal cancer (CRC) is a disease of the older patients, older patients are under-represented from randomized trials. Herein we conducted a retrospective analysis for the effect of panitumumab in the management of older patients (≥65 years) patients with metastatic CRC (mCRC) in the Hellenic Oncology Research Group's (HORG) database.Τhe efficacy of panitumumab-based chemotherapy as front-line treatment in older patients with mCRC was assessed.In total, 110 older patients with KRAS exon 2 wild type tumors were treated with chemotherapy plus panitumumab. The median age was 74 years; 69.9% of the patients were male, with left-sided primary tumors (78.2%), ECOG Performance Status 0-1 (95.4%) and median number of metastatic sites 2. Sixty-two (Overall Response Rate-ORR: 56.4%; 95% CI: 48.8%-68.1%) achieved an objective response, while 21 (19.1%) had stable disease. Median Progression free survival (PFS) was 9.4 months (95% CI: 7.8-11.0 months) and median Overall survival (OS) 23.0 months (95% CI: 20.6-25.3 months). Additionally, a statistically significant difference in ORR (62.7% vs. 33.3%; p = .014), median PFS (12.9 vs. 5.7 months; p = .001) and median OS (31.6 vs. 16.7 months; p .001) was observed in patients with left-sided compared to right-sided primary tumor. There was no treatment-related death. Grade 3-4 toxicities were neutropenia (8.9%) and diarrhea (14.5%) whereas skin rash grade 2 or 3 was recorded in 41.1% and 10.7%, respectively.The results of this retrospective study provide the evidence that combination chemotherapy plus panitumumab is active and well tolerated in older patients with mCRC.

3500 Background: The IDEA aimed to investigate whether a 3-month (3M) of oxaliplatin/fluoropyrimidines-based adjuvant chemotherapy (CT) is non-inferior to the 6-month (6M) in 3-year disease free survival (DFS) in stage high risk stage II and in stage III colon cancer (CC). Methods: HORG-IDEA randomized patients between 3M and 6M of CT with FOLFOX4 or CAPOX with primary end point the 3 years DFS (3yDFS). Results: In total 1121 patients, 413 with high risk stage and 708 with stage IIICC, were randomized between May 2009 and October 2015. The median follow-up was 67 (38-126) months. There were 79 DFS events (43 in 3M and 38 in 6M arm) in high risk stage II patients leading to 3yDFS rate of 82.7 and 83.4% for 3M and 6M, respectively (HR: 1.05; 95%CI: 0.68-1.63, p = 0.829). Similarly, 214 DFS events (161 in 3M and 153 in 6M arm) has been recorded in stage III patients, leading to a 3yDFS rate of 72.9% in the 3M vs. 74.1% in the 6M (HR = 1.06; 95%CI: 0.81–1.42, p = 0.622). For high risk stage II patients receiving FOLFOX4, 3yDFS rate was 76.7% in the 3M vs.79.3% in the 6M (HR = 1.21; 95%CI: 0.54–2.70 p = 0.641). For high risk stage II patients receiving CAPOX 3-year DFS rate was 85.4% in the 3M vs. 83.8% in the 6M (HR = 0.99; 95%CI: 0.59–1.67 p = 0.968). For stage III CC patients receiving mFOLFOX6, 3-year DFS rate was 71.5% in the 3M vs.77.3% in the 6M (HR = 1.18; 95%CI: 0.74–1.86 p = 0.479). For stage III CC patients receiving CAPOX 3-year DFS rate was 74.5% in the 3M vs. 74.7% in the 6M (HR = 0.99; 95%CI: 0.70–1.44 p = 0.991). Conclusions: The results of the HORG-IDEA study are in line with those of the global IDEA project, indicating that 3yDFS is depended on the administered adjuvant regimen, and the choice of regimen and duration should be personalized. Clinical trial information: NCT01308086.

e23150 Background: Cancer is associated with thrombosis due to different pathophysiological processes. CAT is the 2nd cause of death in oncology patients and can occur anytime during the natural history of cancer. CAT is not rare complication, can delay anti-cancer therapy and increase health systems costs. Methods: A prospective observational study (Greek Management of Thrombosis-GMaT) conducted by HeSMO in Greek Oncology units for two years aiming to record clinical practice of CAT management. Patients with active cancer who received CAT treatment or thromboprophylaxis were enrolled after signing informed consent. Results: 546 patients were enrolled from 18 oncology units. Primary cancers were: lung 23.9%, pancreas 13.3%, breast 7.6%, colorectal 8.9%, stomach 8.3%, ovarian 7.6% and other 30.5%. 120 patients received LMWH for Venus Thombo-Embolism (VTE) treatment (Group A) and 426 for thromboprophylaxis (Group B). Group A: 89/120 (74.17%) patients continued in 2nd year and 58.6% received CAT treatment (6.9±4.4 months). Only 2 had VTE recurrence in 2nd year (versus 3 in 1st year). 4/120 (3.33%) had bleeding events (grade 1) in 1st year while no bleeding events occurred in 2nd year. Group B: 345/426 (80.98%) patients continued in 2nd year. 126 (30%) had Khorana score ≥3 and 300 (70%) had Khorana score ≤2. In 2nd year, 123 (35.65%) received thromboprophylaxis (7.3±3.7 months) while 79.4% of them were initially treated with High Thrombotic Treatment Agents (HTTA: e.g. platinum, 5-FU) and 83.1% had metastatic disease. In 2nd year, 52.5% received LMWHs at prophylactic dose and 47.5% at therapeutic dose. Overall, 12 (2.82%) had thrombotic events whereas 4 were recorded in 2nd year. Notably, patients treated with therapeutic doses had lower probability to have a thrombotic event (OR: 5.8, 95% CI: 1.7 to 20.5, p < .05). Six (1.41%) bleeding events (grade 1) occurred in 1st year and one (0.81%) in 2nd year. Conclusions: LMWHs can be used for long term CAT management. Therapeutic LMWHs doses as thromboprophylaxis are safe and effective. Khorana score is a useful model for CAT risk assessment but some other factors such as disease stage and HTTA might be taken into account. CAT can occur anytime during the natural history of cancer. Oncologists should be aware about CAT and its negative influences in patients’ prognosis and quality of life.

5562 Background: The standard of care for Epithelial Ovarian cancer (EOC) is the combination of a taxane plus a platinum compound (TC) whereas the addition of bevacizumab (bev) to this regimen (TC-bev) has been shown to improve the PFS. Patients (pts) with ascites have more aggressive disease and less overall survival. The aim of the study was to evaluate the safety of the TC/bev regimen in the real life clinical practice. Methods: A multi-center observational study, approved by the ethics committees of the participating centers, including 314 pts with stage III/IV EOC, was conducted (11.2011-06.2014) in Greece. Two independent cohorts, with similar clinico-pathologic characteristics, were treated with front-line TC (n = 109) or TC/bev (n = 205) according to the physician’s choice. 83 (40.5%) and 40 (36.7%) in the TC/bev and TC groups presented with ascites. Results: Disease control was achieved in 90.7% and in 78.9% of patients treated with TC/bev and TC, respectively (p = 0.003). Pts with ascites treated with TC/bev experienced a better overall response rate (ORR) (68.7% Vs 55%) and less progression disease (PD) compared to patients receiving TC (13.2% Vs 30.8%). The median PFS in all pts was 21.5mo and 12.4mo (p < 0.001) and median PFS in ascites pts was 18.1mo and 10.3mo in the TC/bev and TC cohort , respectively (p < 0.001). The median OS was not reached in the TC/bev group and it was 36.9mo in the TC group, ( p = 0.059) while in the ascites pts also has not reached and it is 22.5m, respectively ( p = 0.023). The 3 year survival rate in all pts was 59.4% and 50.4% and in ascites pts was 55.3% and 30% in the TC/bev and TC respectively. Neutropenia was the most common grade 3/4 adverse event in 16.6% and 9.1% in TC/bev- and TC- treated patients ( p = 0.072) with no other adverse events > 5%. Conclusions: These real life data demonstrate that the combination of TC/bev represents an active and well tolerated regimen offering survival benefit in patients with stage III/IV EOC and especially in patients with ascites. Additional larger prospective studies are required to confirm these observations. Clinical trial information: NCT01982500.

Purpose: To compare the efficacy of dose dense docetaxel versus paclitaxel following FEC as adjuvant chemotherapy in node positive early breast cancer. Patients and treatment: Women 18–75 years old with histologically confirmed HER2-negative invasive breast carcinoma surgically resected with at least one infiltrated axillary lymph node and absence of metastatic disease were randomized to receive 4 cycles of fluorouracil (700mg/m2), epirubicin (75mg/m2), cyclophosphamide (700mg/m2) followed by 4 cycles of either docetaxel (75mg/m2) or paclitaxel (175mg/m2). All chemotherapy cycles were administered every 14 days with G-CSF support. Stratification was based on menopausal status, number of involved nodes and hormone receptor expression. The primary endpoint of the study was to compare the disease-free survival (DFS) at 3 years and 239 patients were scheduled to enroll on each arm. Results: Between 2004–2007, 481 women were randomized and received FEC followed by docetaxel (arm A; n=240) or paclitaxel (arm B; n=241). The median age was 55 years in both arms, premenopausal status 31.3% versus 32.8%, more than 10 involved axillary nodes in 12.9% versus 12.4%, histological grade 3 tumor in 36.3% versus 35.3% and hormone receptor negative disease in 14.6% versus 12% of patients in arms A and B, respectively. After a median follow up of 56.3 and 55.6 months (p = 0.3) for arms A and B, respectively, there were 42 (17.5%) versus 47 (19.5%) disease relapses (p = 0.5) and 20 (8.3%) versus 22 (9.1%) disease-related deaths (p = 0.7), respectively. The 3-year DFS rates were 88.1% versus 87.3% for arms A and B, respectively. Toxicity included grade 2–4 neutropenia in 31% versus 21% (p = 0.01), thrombocytopenia 3.5% versus 0.8% (p = 0.06), febrile neutropenia 2.1% versus 1.2% (p = 0.5), diarrhea 3.7% versus 2.5% (p = 0.4), neurotoxicity 2.9% versus 4.6% (p = 0.3) of patients in arms A and B, respectively. There were no toxic deaths. Conclusion: The dose dense administration with G-CSF support of FEC followed by either docetaxel or paclitaxel as adjuvant chemotherapy in women with node positive early breast cancer is well tolerated and results in a similar 3-year DFS rate. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-13-09.

Objective: To investigate the resource use and costs associated with the management of metastatic anaplastic lymphoma kinase inhibitors (ALK+) NSCLC in Greece. Methods: The resource use was based on the outcomes of a Delphi panel with seven oncologists and unit costs derived from officially published sources. Results: The average per patient cost in the current treatment pathway (chemotherapy, crizotinib, chemotherapy, palliative care) was estimated at €67,391. The average per patient cost in future scenario 1 (crizotinib, ceritinib, chemotherapy, palliative care) was estimated at €104,571 (treatment duration 26 months) while in future scenario 2 (chemotherapy, ceritinib, chemotherapy, palliative care) was estimated at €134,215 (treatment duration 29.3 months). Conclusion: Ceritinib as second line treatment leads to an increase in total costs reflecting the longer survival

Background: State health insurance authorities in Greece do not reimburse genetic testing for cancer predisposition. The Hellenic Society of Medical Oncology has launched and carries out a national program covering genetic testing for BRCA1/2 mutations detection, with the financial support of pharmaceutical industry. Aim: This analysis evaluates how, during this program, access to genetic testing transformed the oncologists' therapeutic approach toward their ovarian cancer patients and how the results impacted treatment decisions concerning PARP inhibitors. Adoption of testing by healthy relatives and timing of testing in the disease continuum were also evaluated. Methods: Adult patients with high-grade epithelial ovarian carcinoma, irrespectively of family history or age at diagnosis were eligible for this program. Genetic counseling was recommended before testing, and both were offered at no financial cost. First degree family members of pathogenic mutation carriers were also offered free counseling and testing. Results: From March 2015 through January 2018, 708 patients were enrolled and tested. One hundred and forty seven (20.7%) mutation carriers were identified, 102 (14.4%) in BRCA1 and 45 (6.3%) in BRCA2 gene. Testing was more often pursued at initial diagnosis (61%) than at recurrence (39%), as recorded for 409 patients with available relevant information. During the 1st year of the program, average monthly tests performed were 25.1, while during the 3rd year this number increased to 34.3 tests per month. Among patients who tested positive for deleterious BRCA1/2 mutations, relapse was reported in 58 patients, 94.8% of which (n= 55) received treatment with the PARP inhibitor olaparib as per its indication. Family members of 21 patients (14.3%), out of the 147 who tested positive, received genetic counseling and testing for the mutation identified in the context of the program. Conclusion: Free access to genetic testing for BRCA1/2 for ovarian cancer patients and genetic consultation facilitates testing uptake, affects common clinical practice & has major impact on patients and their families. Still, diffusion of genetic information and broader testing of family members require further efforts by the oncological community.

e18868Background: Cancer has multiple processes that increase thrombogenicity. Thrombosis is the 2nd cause of death in cancer patients. CAT is common, could delay anti-cancer therapy and increase c...

e15521Background: Bevacizumab (BEV) is an active antiangiogenic agent for the treatment of all patients (pts) with advanced colorectal cancer (CRC). We investigated the toxicity, compliance and sur...

Purpose: The aim of this study was to explore the effect of dose-dense sequential chemotherapy with or without paclitaxel primarily on disease-free survival (DFS) and secondarily on overall survival (OS) in patients with high-risk operable breast cancer. Patients and methods: From June 1997 until November 2000, 604 patients with T1–3N1M0 or T3N0M0 tumors were randomized to three cycles of epirubicin 110 mg/m2 followed by three cycles of paclitaxel 250 mg/m2 followed by three cycles of ‘intensified’ CMF (cyclophosphamide 840 mg/m2, methotrexate 47 mg/m2 and fluorouracil 840 mg/m2) (group A), or to four cycles of epirubicin followed by four cycles of CMF, as in group A (group B). All cycles were given every 2 weeks with granulocyte colony-stimulating factor support. Results: A total of 595 patients were eligible. Median follow-up was 61.7 months for group A and 62 months for group B. The 3-year DFS was 80% in group A and 77% in group B. Survival rates were 93% and 90%, respectively. The effect of treatment on the hazard of death was different according to hormonal receptor status. More specifically, in patients with negative receptor status the hazard of death was significantly higher for group B (hazard ratio 2.42). Both regimens were well tolerated and severe acute side-effects were infrequent. No cases of severe cardiotoxicity or acute leukemia were recorded. Conclusions: The present study failed to demonstrate a significant difference in DFS or OS between the two treatment groups. However, our study has shown clearly that high-dose paclitaxel can be safely incorporated to dose-dense sequential chemotherapy.

740 Background: The International Duration Evaluation of Adjuvant (IDEA) collaboration was established to prospectively analyze data from six randomized trials to assess whether a 3-month course of oxaliplatin/fluoropyrimidines (FU)-based adjuvant chemotherapy (CT) is non-inferior to the 6-month current standard treatment in stage III colon cancer (CC). The primary endpoint of IDEA was 3-year disease-free survival. The accrual goal for the Greek IDEA study was 1.000 patients. Methods: Greek IDEA randomized patients with stage III colon cancer between 3 months (arm A) and 6 months (arm B) of adjuvant CT with modified (m) FOLFOX6 or XELOX (depending on physician/patient choice). Toxicity was graded during treatment and follow-up using NCI-CTCAE v3.0. Results: From May 2009 to October 2015, 708 patients were randomized in Greek centers either to arm A (n = 354, 50%) or to arm B (n = 354, 50.%). 297 (41.9%) patients received mFOLFOX6 and 411 (58.%) XELOX. The median age was 67 years (20-75) and 579 (81.8%) of them had PS 0. The patients’ population was balanced for the major risk factor between the two arms: N1/N2 disease (68.1/31.9% vs. 68.9/31.1 for ARM A and B, respectively), obstruction (4.5% vs. 2.5 for ARM A and B, respectively) and perforation (5.1% vs. 6.2 for ARM A and B, respectively). Overall, 96.9% and 89.5% of patients completed 3 months (arm A) and 6 months (arm B) of CT, respectively. Median oxaliplatin dose was 505 mg/m2 in arm A and 738 mg/m2 in arm B. Toxicity profiles were comparable between the two arm and the two fluoropyrimidines backbones with a total incidence of Grade 3/4 adverse events 18.9/4.4% and 19.7/5.1% for mFOLFOX6 and XELOX, respectively. Grade 2/3-4 peripheral neuropathy during the study was similar between arm A (33.9/4%) and B (38.7/3.7%). Conclusions: Both mFOLFOX6 and XELOX were safe. More patients completed the scheduled treatment in the 3-arm schedule.

Aims and Background To improve local control in patients with locally advanced inoperable head and neck cancer we administered carboplatin concurrently with radiation. Methods Thirty-nine patients entered the study. There were 35 men and 4 women with a median age of 58 years (range, 24-74) and a median performance status of 90 (range, 60-100) of the Karnofsky scale. The primary site included nasopharynx (5 patients), oropharynx (n=10), hypopharynx (n=5), larynx (n=12), oral cavity (n=2), paranasal sinuses (n=3), salivary glands (n=1) and unknown (n=1). Histology was squamous cell carcinoma in all cases. All patients were irradiated with a 60Co unit. According to the protocol, they should receive 66-70 Gy to the tumor area and 45 Gy to the tumor-free area of the neck. Carboplatin was administered at a dose of 400 mg/m2 on days 2, 22 and 42. Results Totally, 112 cycles of carboplatin were administered, of which 106 (95%) were at full dose. Median dose intensity of carboplatin actually delivered was 170 mg/m2/week (range, 57-200). All patients were irradiated, although only 30 (77%) received >66 Gy. After the completion of combined treatment, 23 (59%, 95% C.I. 42-74%) achieved a CR and 10 (26%, 95% C.I. 13-42%) a PR. Grade 3-4 myelotoxicity was noticed in 60% of the patients. Other grade 3-4 toxicities included stomatitis (13%), dysphagia (5%) and weight loss (3%). Median time to progression was 18 months (range, 2-25). Conclusions Radiation and concurrent administration of carboplatin determined a high CR rate in patients with HNC, although the superiority of this combined modality approach over radiation alone has to be proven in phase III trials.

Forty-nine patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) were treated with 3 cycles of induction chemotherapy prior to definitive local treatment (surgery and/or radiation therapy). Chemotherapy consisted of carboplatin 300 mg/m2 on day 1, fluorouracil 1000 mg/m2 daily as a continuous infusion on days 1 to 5 and high-dose methotrexate 1.2 g/m2 with leucovorin rescue on day 14. After completing the induction chemotherapy, 9 patients (18%) achieved a complete remission (CR), 26 (54 %) a partial remission (PR), 7 had stable disease and 7 a progression. The response rates increased to 53 % CR and 18 % PR following locoregional treatment. Survival at 12 months was 61 % and its actuarial probability at 24 months 31 %. Median time to progression was 14 months. Toxicity from chemotherapy was generally mild. Nausea was observed in 35 %, vomiting in 26 %, stomatitis in 57 %, anemia in 22 %, leukopenia in 36%, thrombocytopenia in 26% and diarrhea in 6% of the patients. In conclusion, the combination of carboplatin, 5-day continuous-infusion fluorouracil and mid-cycle high-dose methotrexate is a moderately effective, well tolerated regimen in patients with SCCHN but does not seem superior to the combination of carboplatin and fluorouracil only.

Fifty-two women with advanced breast cancer were treated with 6 cycles of epirubicin. Even though the study was started with a dose schedule of 110 mg/m2 every 3 weeks, the average treatment interval was 26 days and the median weekly dose 78% of the protocol requirement. Forty-eight patients were evaluable for response; 3 achieved a complete remission which lasted for 17, 24 and 65 weeks, respectively, and 14 a partial remission. Median survival was 32 weeks. Toxicity included nausea/vomiting (68%), anemia (24%), leukopenia (37 %), thrombocytopenia (8 %), alopecia (81 %), stomatitis (24%), diarrhea (14%), fever (19%) and fatigue (14%). Also 1 treatment-related death occurred and 2 cases of arrhythmia. Monotherapy with high doses of epirubicin has definite activity in advanced breast cancer and deserves further study in combination with hematopoietic growth factors which might allow a higher dose Intensity.

BACKGROUND: A randomized phase III trial in high-risk breast cancer patients was conducted, to further explore the impact of dose-density in the adjuvant treatment for breast cancer. The safety analysis is presented. PATIENTS AND METHODS: From October 2000 until June 2005, 1121 node-positive patients were randomized to sequential dose-dense epirubicin 110 mg/m(2) and paclitaxel (Taxol, Bristol Myers-Squibb, Princeton, New Jersey, USA) 250 mg/m(2) (group A), or concurrent epirubicin 83 mg/m(2) and paclitaxel 187 mg/m(2) (group B), both followed by three cycles of 'intensified' combination chemotherapy with cyclophosphamide, methotrexate and fluorouracil (CMF). Granulocyte colony-stimulating factor was given prophylactically with the dose-dense treatments. RESULTS: Median dose intensity of epirubicin and paclitaxel was double in group A, as designed, with significantly less cycles administered at full dose (P < 0.001). Median cumulative dose of all drugs and total treatment duration, however, were identical between groups. Severe taxane-related toxic effects were more frequent in group A, while severe thrombocytopenia was low and present only in group A. There were no differences in the rates of other hematological toxic effects, including febrile neutropenia. The rates of secondary malignancies were low. CONCLUSION: Both regimens as used in the present study are well tolerated and safe. The rates of severe taxane-related toxic effects and thrombocytopenia, although low overall, are significantly increased with the dose-dense sequential regimen. Ann Oncol

Summary Purpose To assess the efficacy and tolerance of the vinorelbine/cisplatin combination in non-small cell lung cancer patients pre-treated with a taxane-based regimen. Patients and methods Among the 32 enrolled patients, 28 (87.5%) had a PS (WHO) of 0–1 and 13 (40.6%) have previously received both platinum compounds and taxanes. Vinorelbine (25mg/m 2 on days 1 and 8) was given by a rapid IV infusion and cisplatin (80mg/m 2 on day 8) after appropriate hydration. The treatment was repeated every 3 weeks. Results A partial response was achieved in six patients (ORR=18.8%; 95% confidence interval: 5.23–32.27); 13 (44.8%) and 10 (34.5%) patients had stable and progressive disease, respectively (intention-to-treat analysis). Four partial responses were observed in patients who were previously treated with taxanes/platinum-containing regimens. The median time to tumor progression was 4.7 months (range, 1.3–15.4). After a median follow-up period of 6.3 months (range, 1.3–15.4) the median overall survival was 7.6 months and the 1-year survival rate 17.7%. Grade 3 and 4 granulocytopenia was observed in 11 (34.4%) patients and grade 4 thrombocytopenia in one (3.1%). Eleven (34.4%) patients presented grade 2 and 3 anemia. Febrile neutropenia occurred in one (3.1%) patient. Grade 3 and 4 nausea/vomiting was reported in one (9.3%) patient each and grade 2 fatigue in four (12.5%). Conclusions The combination of vinorelbine and cisplatin is an active and well tolerated salvage regimen in NSCLC patients pre-treated with taxane-based chemotherapy.

Background To compare survival between patients with advanced breast cancer (ABC) treated with epirubicin/paclitaxel (Taxol) or paclitaxel/carboplatin (Cp) chemotherapy. Patients and methods From January 1999 to April 2002, 327 eligible patients with ABC were randomized to receive either paclitaxel 175 mg/m2 in a 3-h infusion followed by epirubicin (EPI) 80 mg/m2 (group A) or paclitaxel, as in group A, followed by Cp at an AUC of 6 mg × min/ml (group B) every 3 weeks for six cycles. Results After a median follow-up of 23.5 months, median survival was not significantly different between the two groups (22.4 months versus 27.8 months, P=0.25), whereas median time to treatment failure was significantly longer in patients treated with paclitaxel/Cp (8.1 months in group A versus 10.8 months in group B, P=0.04). Both regimens were well tolerated. In total, 39 patients (24%) in group A and 46 (29%) in group B suffered at least one severe side-effect. Quality-of-life assessment and cost analysis did not reveal any significant differences between the two groups. Conclusion Our study suggests that the paclitaxel/Cp combination is an effective therapeutic alternative for patients with ABC in which anthracycline administration has the potential of being harmful.

1077 Background: Early breast cancer is a heterogeneous disease, and, therefore, prognostic tools have been developed to evaluate the risk for distant recurrence. We compared the Clinical Treatment...

Twenty-two patients with supratentorial malignant gliomas were treated postoperatively with concurrent intracarotid chemotherapy and radiation therapy. There were seven women and 15 men with a median age of 56 years (range, 22-69) and median performance status (Karnofsky score) of 70 (range, 40-90). In all except two cases, histologic studies confirmed malignant glioma. All patients were irradiated with a cobalt 60 equipment. They should have received 45 Gy to the whole brain plus a 15-Gy coned-down boost to the tumor area. Chemotherapy consisted of cisplatin infusion at a dose of 60 mg/m2 on days 2, 22, and 42. Treatment was interrupted in two patients because of progressive disease and voluntary withdrawal in one patient each. In all, 63 courses of cisplatin infusion were administered, all at full dose. Two patients achieved a partial response, and nine had stable disease. Toxicities included nausea/vomiting in nine patients (41%) and transient hemiparesis, confusion, diarrhea, and thrombophlebitis in one patient each. Median time to progression was 26 weeks (range, 4-226+), and median survival was 58 weeks (range, 14-226+). In conclusion, the present study suggests that intracarotid cisplatin administered concurrently with radiation does not improve the therapeutic index in malignant gliomas.

To improve local control in patients with locally advanced inoperable head and neck cancer we administered carboplatin concurrently with radiation.Thirty-nine patients entered the study. There were 35 men and 4 women with a median age of 58 years (range, 24-74) and a median performance status of 90 (range, 60-100) of the Karnofsky scale. The primary site included nasopharynx (5 patients), oropharynx (n = 10), hypopharynx (n = 5), larynx (n = 12), oral cavity (n = 2), paranasal sinuses (n = 3), salivary glands (n = 1) and unknown (n = 1). Histology was squamous cell carcinoma in all cases. All patients were irradiated with a 60Co unit. According to the protocol, they should receive 66-70 Gy to the tumor area and 45 Gy to the tumor-free area of the neck. Carboplatin was administered at a dose of 400 mg/m2 on days 2, 22 and 42.Totally, 112 cycles of carboplatin were administered, of which 106 (95%) were at full dose. Median dose intensity of carboplatin actually delivered was 170 mg/m2/week (range, 57-200). All patients were irradiated, although only 30 (77%) received66 Gy. After the completion of combined treatment, 23 (59%, 95% C.I. 42-74%) achieved a CR and 10 (26%, 95% C.I. 13-42%) a PR. Grade 3-4 myelotoxicity was noticed in 60% of the patients. Other grade 3-4 toxicities included stomatitis (13%), dysphagia (5%) and weight loss (3%). Median time to progression was 18 months (range, 2-25).Radiation and concurrent administration of carboplatin determined a high CR rate in patients with HNC, although the superiority of this combined modality approach over radiation alone has to be proven in phase III trials.

In an attempt to improve local control of locally advanced head and neck cancer, radiation therapy was combined with cisplatin. Forty-eight patients entered into this study. All patients were irradiated with a 60Co unit and according to the protocol they should receive 70 Gy in the tumor area and 45 Gy in the rest of neck. Cisplatin was administered at a dose of 100 mg/m2 on days 2, 22 and 42. Thirty-seven (80%) patients received the total radiation dose as initially planned. Thirty-four (72%) patients achieved complete and 5 (10%) partial response. Grade 3-4 toxicities included vomiting (14%), stomatitis (4%), diarrhea (2%), myelotoxicity (14%), hoarseness (4%), dysphagia (30%), weight loss (32%), nephrotoxicity (4%) and dermatitis (2%). After a median follow-up of 26 (range, 18-33) months, 16 patients have died. Among the 35 complete responders 6 later on relapsed. Median relapse-free survival has not yet been reached. Combined radiation therapy and cisplatin appears to be a highly active treatment in patients with advanced head and neck cancer as far as primary locoregional response is concerned.

The prognosis of patients with locally advanced head and neck cancer (HNC) is generally poor. Despite mutilating surgery and/or radical irradiation, 50–60 % of patients recur within 2 years and an additional 20–30 % develop distant metastases [1].

Forty-nine patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) were treated with 3 cycles of induction chemotherapy prior to definitive local treatment (surgery and/or radiation therapy). Chemotherapy consisted of carboplatin 300 mg/m2 on day 1, fluorouracil 1000 mg/m2 daily as a continuous infusion on days 1 to 5 and high-dose methotrexate 1.2 g/m2 with leucovorin rescue on day 14. After completing the induction chemotherapy, 9 patients (18%) achieved a complete remission (CR), 26 (54%) a partial remission (PR), 7 had stable disease and 7 a progression. The response rates increased to 53% CR and 18% PR following locoregional treatment. Survival at 12 months was 61% and its actuarial probability at 24 months 31%. Median time to progression was 14 months. Toxicity from chemotherapy was generally mild. Nausea was observed in 35%, vomiting in 26%, stomatitis in 57%, anemia in 22%, leukopenia in 36%, thrombocytopenia in 26% and diarrhea in 6% of the patients. In conclusion, the combination of carboplatin, 5-day continuous-infusion fluorouracil and mid-cycle high-dose methotrexate is a moderately effective, well tolerated regimen in patients with SCCHN but does not seem superior to the combination of carboplatin and fluorouracil only.