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Purpose: To test the hypothesis that therapy of intermediate- and high-grade (excluding Burkitt lymphoblastic) lymphoma with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) could be safely dose-intensified with routine filgrastim support. Patients and Methods: Eligible patients were those who were previously untreated and who had either bulky stage II, or stage III or IV lymphoma with working formulation histology D, E, F, G, H, or J; performance status ≤ 2; and acceptable end organ function. No upper age limit was specified. Therapy was dose-intensified CHOP (CHOP-DI) with filgrastim support. Each course was repeated every 14 days for six planned courses. Results: Eighty-eight eligible patients were treated with CHOP-DI and had a median follow-up of 5.1 years on this phase II study, designated Southwest Oncology Group (SWOG) 9349. The progression-free survival was 51% at 2 years and 41% at 5 years. The overall survival was 60% at 5 years. Three fatal treatment-related events occurred. One patient with myelodysplastic syndrome was reported. Conclusion: Treatment with CHOP-DI can be safely administered in the cooperative group setting and results in improved survival. Estimated overall survival at 5 years was 14% better than that of patients treated with standard-dose CHOP in an earlier SWOG study, although progression-free survival of 60% at 2 years—the prespecified end point—was not achieved. CHOP-DI, given every 2 weeks at escalated doses, is a strategy that should be tested in a future randomized clinical trial in lymphoma.

Purpose: To determine the efficacy of combination fludarabine and mitoxantrone (FN) in untreated stages III and IV low-grade lymphoma. The major end point was to estimate progression-free survival (PFS) in all eligible patients. Patients and Methods: Seventy-eight eligible patients were registered. Chemotherapy courses were administered every 4 weeks with mitoxantrone 10 mg/m2 on day 1 and fludarabine 25 mg/m2 on days 1, 2, and 3 for a total of six to eight cycles. Pneumocystis carinii prophylaxis was required. Results: Seventy-three patients (94%) attained an objective response. Complete remission was demonstrated in 34 patients (44%) and partial remission was demonstrated in 39 patients (50%). With a median follow-up time of 5.5 years, the median PFS was 32 months, with a 4-year PFS rate of 38%. Median survival has not been reached and 88% of all patients are alive at 4 years. The application of the International Prognostic Index and serologic staging showed significant differences in PFS in all risk groups, whereas overall survival was markedly worse for the highest-risk group in either prognostic model. Three prior Southwest Oncology Group trials using a regimen of cyclophosphamide, doxorubicin, vincristine, and prednisone or a combination of prednisone, vincristine, methotrexate, cytarabine, cyclophosphamide, etoposide, nitrogen mustard, vincristine, procarbazine, and prednisone in similar patient populations demonstrated comparable clinical outcome, although the 4-year survival for FN was better. FN was well tolerated, but mild to severe reversible myelosuppression was noted. Other complications were rare. Conclusion: FN is an effective, safe chemotherapy combination for patients with advanced-stage, low-grade lymphoma. Clinical outcomes were comparable to prior published data using anthracycline-based regimens.

PURPOSE Cisplatin has played a major role in the treatment of non-small-cell lung cancer (NSCLC). This randomized trial was performed by the Southwest Oncology Group (SWOG) to determine whether the combination of vinorelbine and cisplatin has any advantage with regard to response rate, survival, and time to treatment failure over single-agent cisplatin in the treatment of patients with advanced NSCLC. METHODS Between October 1993 and April 1995, 432 patients with advanced stage NSCLC were randomized to receive arm I (cisplatin 100 mg/m2 every 4 weeks) or arm II (cisplatin 100 mg/m2 every 4 weeks and vinorelbine 25 mg/m2 weekly). All patients were chemotherapy-naive, had performance status (PS) 0 or 1, and had adequate hematologic, renal, and hepatic function. RESULTS Four hundred fifteen patients were eligible and assessable. On arm I (cisplatin), there was a 12% partial response rate. Arm II (cisplatin and vinorelbine) had a 26% response rate (2% complete responses and 24% partial responses, P = .0002). There was a statistically significant advantage with regard to progression-free survival (median, 2 v 4 months; P = .0001) and overall survival (median, 6 v 8 months; P = .0018) for the cisplatin and vinorelbine arm. One-year survival was 20% for cisplatin alone and 36% for the combination arm. There was more hematologic toxicity on arm II of the study (81% grades 3 and 4 granulocytopenia v 5% on arm I). Other toxicities, such as renal insufficiency, ototoxicity, and nausea and vomiting, and neuropathy were similar. CONCLUSION The results of this study indicate that the combination of cisplatin and vinorelbine is a superior treatment when compared with single-agent cisplatin in the treatment of advanced NSCLC. Cisplatin and vinorelbine is the new standard for SWOG against which new therapies will be evaluated.

10704 Background: A previous study with weekly gemcitabine and monthly docetaxel at 100 mg/m2 yielded a 79% response rate and a median survival of 24 months. (Laufman, Ann Oncology 2001; 12:1–6). This study was designed to see if the efficacy to toxicity ratio could be improved by decreasing the docetaxel dose to 75 mg/m2. Methods: Gemcitabine and docetaxel were given to 25 patients, all of whom had received prior chemotherapy. Nine had had taxanes, more than 12 months before entry. A maximum of 6 cycles of gemcitabine 800 mg/m2 on days 1, 8 and 15 and docetaxel 75 mg/m2 on day 1 were given every 28 days. Prophylactic antibiotics were given during neutropenia. Growth factors were used for anemia, neutropenia, or for secondary neutropenic prophylaxis. Maintenance therapy consisting of gemcitabine 800 mg/m2 on days 1, 8 and 15 every 28 days was given to 12 patients, 2 of whom also received consolidation radiation. Results: A total of 122 cycles of induction therapy were given, with 14 patients receiving all 6. Dose delivery was 91.9% for docetaxel and 70.2% for gemcitabine. A total of 43 maintenance cycles were given, ranging from 1 to 12 cycles per patient. Dose delivery was 70.6%. Toxicity consisted of myelosuppression and fatigue. Grade 4 neutropenia occurred in 20 patients but was complicated by infection or fever in only 3. Five patients had grade 3 anemia and 4 had grade 3 thrombocytopenia. Other grade 3 toxicities consisted of fatigue in 8 patients, myalgia/arthralgias in 4, mucositis in 1, pneumonia in 1 and diarrhea in 1. Responses defined by RECIST criteria occurred in 12 patients (48%), including 8 of 16 taxane-naïve and 4 of 9 taxane-exposed patients. Conclusion: This regimen is active, and the most common toxicity is asymptomatic neutropenia. Sponsored by Eli Lilly and Aventis. No significant financial relationships to disclose.

7303 Background: Because PS 2 NSCLC pts have poor outcomes with platinum-based chemotherapy, we tested the palliative effects and safety of a non-platinum doublet in a phase II study. Methods: Docetaxel 60 mg/m2 Day 1 and Gemcitabine 800 mg/m2 Days 1, 8 and 15, were given q 4 weeks. Symptomatic responses were assessed q cycle and radiographic tumor responses q 2 cycles. Lung cancer-specific symptom burden and quality of life (QOL) were assessed by patient and observer using the Lung Cancer Symptom Scale (LCSS) and the Subjective Health Estimation (SHE). Results: 30 pts were entered: 17 males, median age 69 yrs, 22 stage IV, 13 with severe cardiorespiratory co-morbidities. Pts received a median of 2 cycles. Toxicities were grade 4 neutropenia (5), febrile neutropenia (1), grade 3 anemia (2), grade 3 asthenia (11). Ten (33%) of pts had partial responses. 21 pts completed baseline QOL assessments with at least one follow-up (F/U). There was no significant difference in age, rate of severe co-morbidities, bas...

8097 Background: A regimen of gemcitabine (G) and docetaxel (T) was tested concurrently in 39 patients with breast and 40 with lung cancer, and different toxicity profiles were observed. Multivariate analysis incorporating cancer type, gender, age and prior treatment showed that grade 4 neutropenia was seen more frequently among non-smokers, (p=0.03). Pharmacokinetic effect of smoking status on the clearance of both drugs was examined. G is cleared via renal excretion, and is affected by age and gender, but not by smoking status. T is metabolized by the enzyme cytochrome p450 3A4 (cyp 3A4), whose activity is not associated with smoking status, as demonstrated by measurement of erythromycin breath tests in a separate cohort of 79 sarcoma patients. Interactions between smoking and absolute neutrophil count (ANC) were investigated further. Methods: Charts of 466 patients treated with G and/or T in a single outpatient facility were reviewed. Cohorts were defined by drug dose and regimen. Within each cohort, m...

7136 Background: Ortataxel is a novel second-generation taxane, with potent growth inhibitory activity against human cell lines that express P-glycoprotein 170. Compared to paclitaxel and docetaxel...