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7506 Background: No standard of care exists for patients with advanced NSCLC and PS 2 and clinical practice ranges from supportive care to combination chemotherapy. Methods: In a Brazilian multicenter phase III randomized trial, advanced NSCLC patients, with any histology at first, amended to non-squamous only, PS 2, no prior chemotherapy, and adequate organ function, were randomized to P alone (500 mg/m2) or CP (AUC 5 + same P) administered every 3 weeks for 4 cycles. Stratification factors included stage (IIIB vs. IV); age (≥70 vs. nd line therapy Conclusions: Combination chemotherapy with CP significantly improves survival, with acceptable safety, in eligible patients with advanced NSCLC and PS 2, and represents a new standard.

e19523 Background: Patients undergoing chemotherapy often complain of alterations of taste (dysgeusia), for which no conventional therapy exists. The African fruit Synsepalum dulcificum, or “Miracle Fruit” (MF), has been described as a powerful taste alteration product, converting sour to sweet taste. We conducted a single institution trial to assess whether the MF improves dysgeusia. Methods: Patients with a performance status of 2 or less, receiving cyclophosphamide, carboplatin, cisplatinum, gemcitibine, methotrexate, doxorubicin, 5-fluorouracil, paclitaxel, docetaxel, vinorelbine, oxaliplatin, irinotecan or etoposide were included in the study if they complained of dysgeusia. Patients were randomized in a crossover fashion to immediately receive the MF for 2 weeks (group A) or to receive the MF after 2 weeks of supportive measures alone (group B). Endpoints were: improvement in taste (study powered to detect 30% response with MF, as measured by the Wickham questionnaire), weight changes, and quality o...

7517 Background: Oncogenic ALK gene rearrangements (rALK) recently have been identified in approximately 3-5% of all NSCLC, particularly in non-smoking patients (pts) with epidermal growth factor r...

8073 Background: IPI-504 (retaspimycin hydrochloride) is a potent, water-soluble heat shock protein 90 (Hsp90) inhibitor. IPI-504 causes the degradation of mutated epidermal growth factor receptor (mtEGFR) kinase and cMET in NSCLC cell lines. IPI-504 also significantly reduces tumor growth in murine xenograft models, including tumors resistant to tyrosine kinase inhibitors (TKIs). Methods: This phase II trial is investigating the safety and antitumor activity of intravenous (IV) 400 mg/m2 IPI-504 given twice weekly for 2 out of 3 weeks. Eligible patients (pts) had stage IIIb (w/ malignant effusion) or stage IV NSCLC that progressed after TKI treatment. EGFR mutation analysis was performed on all pts. Two cohorts (n=10 each) were initially enrolled and stratified by EGFR status (mtEGFR or wtEGFR). Planned cohort expansion to 29 pts occurred if ≥ 1 pt from that cohort had a best response of stable disease (SD) ≥12 wks or partial response (PR). Pts were evaluated for safety and RECIST response every 6 weeks. Central, independent radiology review was performed for all imaging studies. Results: 43 pts have been enrolled: 10 mtEGFR, 17 wtEGFR, 12 pending analysis, and 4 EGFR-failed samples. 19 pts are currently on study. Median age is 62 yrs (range 31–77). Median no. of prior therapies is 3. Common related adverse events are fatigue, nausea, and diarrhea. Anti-tumor activity has been observed, see table. Both cohorts have been expanded. Conclusions: IPI-504 monotherapy has been well tolerated, with evidence of anti-tumor activity, particularly and unexpectedly in the wtEGFR cohort. These data suggest that IPI-504 may have antitumor activity in heavily pretreated pts with advanced NSCLC. Further evaluation continues in the expansion phase of the trial. [Table: see text] [Table: see text]

7567 Background: Myelosuppression is a frequent toxicity of CMT, leading to clinical complications and dose reductions, which may compromise outcome in a potentially curative setting. A randomized ...

6595 Background: Because the elderly are numerically underrepresented in cancer clinical trials, the benefits and toxicities of cancer therapies in the general population of elderly patients is not known. Nevertheless, clinicians need such information. A solution may be found in analyses of observational data. Specific Aim: We performed a criterion validation study to determine the accuracy with which observational Medicare claims data measure clinically significant chemotherapy-related toxicities in elderly Medicare beneficiaries with cancer. Methods: We created a cohort of 175 elderly clinical trial patients treated on two Cancer and Leukemia Group B (CALGB) trials (i.e., 9,344 adjuvant breast and 9,730 advanced lung cancer trials) and merged participants’ CALGB data with their Centers for Medicare and Medicaid Services (CMS) data. From CALGB data, we identified all grade III/IV toxicities with a frequency of ≥3%. We reviewed diagnostic and procedure codes from CMS coding manuals, developed initial algorithms to measure the toxicities and then finalized the algorithms after empiric review of individual patients’ actual CMS codes incurred during the observation period (i.e., date of first trial treatment through 90 days following last trial treatment). We compared results of each of our CMS toxicity algorithms to gold-standard of CALGB grade III/IV toxicity information in order to calculate the CMS algorithms’ test characteristics. Results: The following 15 grade III /IV chemotherapy-related toxicities occurred in ≥3% of the 175 patients: white blood cell, hemoglobin, platelets, anorexia, nausea, vomiting, diarrhea, stomatitis, sensory neuropathy, motor neuropathy, motor or sensory neuropathy, dyspnea, hyperglycemia, infection, and malaise. Of these, only the CMS-based algorithm measuring ‘grade III/IV vomiting‘ had a sensitivity, specificity, and area under the ROC of ≥ 80%. Conclusions: The results of this preliminary study suggest that CMS claims data may be of only limited value in measuring clinically significant chemotherapy- related toxicities in elderly Medicare beneficiaries with cancer. Future research will focus on confirming these findings in a larger and more diverse patient sample. No significant financial relationships to disclose.

7595 Background: There is no standard treatment for patients (pts) with advanced NSCLC and PS 2. Docetaxel (D) is active and well tolerated on a weekly schedule. Cetuximab (C) and Bortezomib (B) are new agents with activity in NSCLC. We explored these two new combinations in PS 2 pts. Methods: In a multi-center randomized phase II trial, untreated pts with advanced NSCLC and PS 2 were randomized to D 30 mg/m2 d1,8,15 q. 28 days in combination with either C 400 mg/m2 week 1 then 250 mg/m2 weekly, or B 1.6 mg/m2 d1,8,15 q. 28 days for 4 cycles. Pts with CR/PR/SD were allowed to continue C or B until PD. The study was non-comparative and the primary endpoint was progression-free survival (PFS) rate at 6 months. The trial had a type I error of 0.0746 and power of 0.9 to differentiate a 6-mo PFS of 42%. Results: 64 pts were enrolled between 7/05 and 9/06. 5 were ineligible and 3 never received protocol treatment. Results are reported for 55 pts (27 D+C; 28 D+B). Most pts had stage IV adenoCa and 13% had brain metastases. Median age was 70 (range, 35–88) and 65% were male. Response: 10.5% for D+C and 13.6% for D+B. Median PFS was 3.1 mo for D+C and 1.8 mo for D+B. PFS rates at 4 mo (data not yet mature for 6-mo): 33% and 28%, respectively. Median survival: 3.8 mo for D+C and 3.3 mo for D+B. Gr 3/4 hematologic toxicity was 17% in both arms. Gr 3/4 non-heme toxicities were 44% in D+C and 36% in D+B arm. 5 pts died of treatment-related toxicities (3 D+C; 2 D+B). Conclusions: These results confirm the poor prognosis associated with a PS of 2. Based on our preliminary analysis, neither combination produced results that justify further research in this subset of patients. The treatment of PS 2 patients with advanced NSCLC remains a vexing problem and new approaches are urgently needed. No significant financial relationships to disclose.

7022 Background: A previous CALGB trial suggested a benefit for carboplatin-paclitaxel (CP) over P alone in pts with PS 2. Erlotinib (E) has activity in previously treated pts with low PS but has not been formally tested in 1st line. Methods: In a multi-center randomized phase II trial, untreated pts with advanced NSCLC and PS 2 were randomized to E 150 mg daily or CP (AUC 6 and 200 mg/m2) for 4 cycles. Pts in CP who progressed, did not tolerate, or refused further therapy were allowed to cross over to E. The primary endpoint was progression-free survival (PFS). QoL analysis was performed in all pts and tumor samples were obtained whenever possible. Results: As of 12/05, 98 of 102 projected pts have been accrued. Results are reported for 88 (46 E; 42 CP). Demographics were balanced except for more females in E (59%) than CP (45%). Most pts had stage IV adenoca histology. Never-smokers comprised 13% and 7% of pts respectively. Response for E: 2% PR and 30% SD; for CP, 10% PR and 45% SD. Gr 2–4 toxicities for E: rash (34%) and diarrhea (11%); for CP: nausea (12%), neuropathy (14%) and fatigue (29%). Median PFS was 2.5 mo for E (95%CI 1.28 - 2.79) and 4.0 mo for CP (95%CI 2.66 - 4.86). Of 42 pts in CP, 21 have crossed over to E. Conclusions: This is the first randomized phase II trial of E in PS 2 patients. Based on preliminary results, PS 2 patients seemed to fare better with standard CP than single agent E as initial therapy. Mature survival and QoL data will be available in June. [Table: see text]

17009 Background: Oxaliplatin-Gemcitabine (GemOx) is an active and well tolerated. Bevacizumab (BV) prolongs survival when combined with carboplatin-paclitaxel. This phase II trial evaluates the efficacy of GemOx + BV as 1st line therapy for advanced NSCLC patients. Methods: Pts with stage IIIB (effusion) and IV non-squamous NSCLC, ECOG PS 0 or 1, no CNS metastasis, and no other contraindications to BV, are eligible. Prior therapy for earlier-stage disease allowed if completed at least 12 months before enrollment. Treatment consists of Gem 1000 mg/m2 on d1 and 8, Ox 130 mg/m2 on d1, and BV 15 mg/kg on d1, repeated every 3 wks for a total 4 cycles. Pts who respond or have stable disease receive BV maintenance until progression. Main endpoints are response rate (RR), grade (Gr) 3–4 toxicities, time to progression (TTP), and overall survival (OS). Results: As of 12/05, 26 out of 50 projected pts have been enrolled from 4 institutions. M/F 17/9; median age 65y (45,81); IIIB/IV 3/23; PS 0/1 8/18. Median F/U time is 3.7 months. 24 pts are evaluable for toxicity: 1Gr3 ANC; 1Gr3 and 4 PLT; no FN.3 Gr3 diarrhea and 2 Gr3 N/V; 1Gr3 and 4 hypophosphatemia; 1 pt had ischemic bowel after the 1st cycle, recovered fully and was removed from study; 1 pt died of liver failure in the 1st cycle. No bleeding complications have occurred. 22 pts are evaluable for RR (ITT): 7 PR (31%); 8 SD (36%). TTP and OS data not yet available. Conclusions: This is the first report of GemOx in combination with BV in advanced NSCLC. This regimen has minimal hematologic toxicity but selected non-hematologic toxicities are noted. Activity appears promising and merits further investigation. Accrual is ongoing. [Table: see text]

7058 Background: Ir in combination with DDP has proven superior to DDP & VP-16 in extensive stage SCLC (Noda et al NEJM 1/02), with marked increase in 2 yr survival (19.5%, vs 5.2%). Hence, it is critical to determine if Ir can be safely & effectively integrated with concurrent RT and DDP in earlier stage, Ltd SCLC. Methods: 1° endpoint: Determine maximum tolerated dose (MTD) of Ir d 1 & 8 plus DDP 60 mg/m2 q 3 wks & either BID RT (45 Gy) or QD RT (70 Gy). Eligibility stipulated Tx-naïve patients (pts) with Ltd SCLC, PS 0–1, adequate heme (ANC ≤ 1500/mL; plts ≥ 120,000/mL) hepatic (bili ≤ 1.5/dL) & renal (creat ≤ 1.5gr/dL) function, & baseline FEV1 of ≥ 1 liter. Ir was escalated in sequential (seq) cohorts from 40 mg/m2 (level 1) to 50 mg/m2 (level 2) & then to 60 mg/m2 (level 3) d 1 & 8 q 3 wks during each cycle of treatment. Ir & DDP were given concurrently with RT for cycle 1 in seq A (45 Gy) & during cycles 1 & 2 in seq B (70 Gy). 36 pts were targeted for accrual. DLT was defined as gr 4 esophagitis, pneumonitis, or diarrhea; gr 4 neutropenic fever, or any attributable gr 5 toxicity Results: As of 12/05, 36 pts were accrued, (21 - seq A; 15 - seq B). Median age was 64 (range 49–79) Of 33 eval pts, 18 (55%) were female; 24 (73%) PS 0; 67% had ≤ 5% wt loss. Attributable DLT was not seen in seq A, but was observed in seq B (70 Gy) at 50 mg/m2 with 1 episode each of gr 4 diarrhea & esophagitis, necessitating hospitalization. In addition, 1 pt in seq B had non-attributable gr 4 cardiovascular AEs. There has been no acute gr 5 toxicity. 1 pt experienced late gr 3 pulm toxicity, another gr 3 constitutional toxicity, including wt loss. The overall incidence of gr 3 esophagitis was 34%. Conclusions: In Ltd SCLC, I at 60 mg/m2 d 1 & 8 is safe & feasible in combination with DDP 60 mg/m2 q 3 wks & BID RT (45 Gy). The MTD for I in combination with RT (70 Gy) & DDP 60 mg/m2 is 40 mg/m2 d 1 and 8. Response, progression, survival data remain immature. [Table: see text] [Table: see text]

7036 Background: A phase II trial was conducted to evaluate the activity of single agent cetuximab in patients (pts) with recurrent NSCLC. Preliminary data was previously reported (Lynch, et al, ab...

6022 Background: We sought to determine the accuracy with which an administrative data source, Medicare claims data, captures chemotherapy use in elderly Medicare beneficiaries with cancer. Methods...

7147 Background: Recent trials have demonstrated the efficacy of chemotherapy in elderly(defined as > age 70) patients(pts) with advanced non small cell lung cancer(NSCLC). The risks/benefits of ch...

7208 Background: Topotecan is approved for the treatment of patients with relapsed SCLC and is the only single agent proven in randomized clinical trials to provide symptom palliation in these pati...

7137 Background: Current 2nd-line treatment options for pts with advanced stage NSCLC are limited. New, more effective, and less toxic agents/combinations are thus needed for treating NSCLC in the ...

Introduction To evaluate the efficacy and safety of myeloid growth factors in patients with locally advanced non-small cell lung cancer treated with combined modality therapy (CMT). Methods Patients with stage IIIA/B non-small cell lung cancer, performance status 0 to 1, and forced expiratory volume in 1 second ≥1.5, received cisplatin 75 mg/m 2 on day 1 + etoposide 80 mg/m 2 on days 1 to 3 every 3 weeks for 2 cycles concurrent with thoracic radiotherapy to 61 Gy. filgrastim 5 mcg/kg/d was administered for 10 days beginning on day 4 of each chemotherapy cycle. Patients without progression received docetaxel 75 mg/m 2 every 21 days for 3 cycles with peg-filgrastim 6 mg on day 2. The primary end point was a 50% reduction in the incidence of grade ¾ neutropenia compared with historical controls. Results A total of 26 eligible patients were enrolled. Median age was 67, 76% were men, and 58% had stage IIIA. Gr3/4 neutropenia during CMT was 19.2% and 3.8%, respectively. There were no episodes of febrile neutropenia. Gr4 thrombocytopenia was 15.4% with 2 patients requiring transfusions. Gr3 esophagitis was noted in 7.7% and Gr ¾ pneumonitis in 21.6% of patients. No patients died of treatment-related toxicities. Dose reductions/delays occurred in 3.8% of patients during CMT. Median progression-free survival and median survival were 10.7 and 27.6 months, respectively. The 1- and 2-year survival rates were 61.5% and 46.2%, respectively. Conclusions Our data suggest that the addition of filgrastim to CMT is safe and effective. The rate of grade ¾ toxicities, including febrile neutropenia, compares favorably to previous trials using a similar regimen. Dose intensity is maintained. This strategy merits further evaluation.

The insulin growth factor pathway (IGF), a complex one with multiple receptors and ligands, is involved in essential steps of cancer development such as survival, proliferation, and metastases.1 Although expression of IGF signaling seems to have prognostic significance, predictive factors for benefit have not yet been identified. Cross talk between the IGF and other pathways, particularly EFGR, may be important for understanding and mitigating resistance. Several compounds, including monoclonal antibodies and tyrosine kinase inhibitors, are currently under clinical investigation for inhibition of the IGF pathway.