Abstracts/Lung Cancer 12 (1995) 265-329 311

with SCLC with citha limited disasc (LD; 276 patients) or good- prognosis cxtcnsivc disease (ED; 162 patients) were randomized. Weekly chcmothcrapy was 12 sltemating cycles of ifosf*mide/doxorubicin and cispl*tin/ctoposidc (FE), while 3-week treatment xv** six alternating cycles of cyclophosphamidci doxorubicin/vincristine (CAV) and PE. Thoracic irradiation was administered 3 weeks after completion of chemotherapy to LD patients who attained 8 complete response (CR) or partial response (PR). Patients were well matched for clinical charactetistics and prognostic factors. Results: Overall response was the wne in both *rms: 82.3% (39.4% CR) with weekly and 81.1% (36.9% CR) with 3-week treatment. The median survival (MS) durations were 10.8 snd 10.6 months for weekly and 3-week chcmothcrapy, respectively. The 2-year survival rates were I I .8% and I I .7% in the weekly and 3-week *rms, respectively. Re~+vcd dose-intensity (DI) was 73.9% of projected for weekly trcntmcnt and 92.7% for 3-week trcatmmt. Hematologic toxicity was the major dose-limiting toxicity for the weekly trcatmcnt. Conclusion: This trial excludes at 90% power * benefit of greater than 10% for t-year survival for weekly treatment. The rcceivcd DI was reduced ta * grcstcr extent with weekly treatment, mainly due to hematologic toxicity.

WsseDstudyoTaewtiwolLPf~ayiatrrvewusinfuajoodrisplatin and etoposide with conawreot chest radiation therapy in limited stage small cell lung cancer Sugita T, Matsunaga K, Kobayashi H, Horikawe S, Suzuki Y, Nishiyama H et al. Depr of Respiratmy Medicine, W-ma Red Cmsr Hospiral Wakayama. Jpn J Cancer Chcmothn 1994;21:2479-83. The eficacy of continuous fiveday intravenous infusion of cisplatin (CDDP) and etqmside with wncurrcnt chest radiation tbcmpy was cveluatcd in patients with limited stage small cell lung cancer. The fti group of patients rcgistcrcd from Fcbrusry 1989 to Scptcmber 1990 reccivcd three course* of chemotherapy (CDDP 20 mg/m*/d*y x 5 days, etoposidc 40 mg/m’/d*y x 5 days) end concurrat chest radiation therapy on the third course with dose reduction of etoposide. The second group of patients rcgistcred afler February 1991 rexivcd four cowses of chemothempy (CDDP 20 mglm’iday x 5 days, etoposide 50 m&‘/day x 5 days) snd concumnt chest radiation thcmpy on the first and second courses with dose reduction of etoposidc. The rcsponsc rates were 91.7% and 93.3% respectively. The median duration of survival was 32.0 months and 20.1 months, respectively. Major toxicity was lcukocytopcnia and 64% and 80% of patients mwuntcrcd lcukocytopenia of Grade 3 or 4. In conclusion these regimens show remarkable efficacy with acceptable toxicity.

Vinorelbine (Navelbiw) in non-small cell lung cancer: FWure direc- tions Crawford J. Depwbnent o$Xfedicine, Carl Bldg Duke lJniversiyh4edicai Cents?< RexaTch ti Durham, NC 27706. Scmin Onwl 1994;2l:Suppl 10:85-8.

Random&d clinical trials of vinorclbinc (Navclbinc; Burroughs Wellcome Co, Research Triangle Park, NC; Pierre Fabrc Medicament. Paris, France) as * single agent and in combination with cisplatin have demonstrated antihunor activity in patients with advanced non-small cell lung cancer (NSCLC). Administered as a single agent on * weekly schedule, the vinorclbine therapeutic profile compares favorably with other regimens currently used in palliative tratmcnt of patients with advanced NSCLC. Vinorelbinc is also being considered in other trcatmmt settings *s well: sdjuvant treatment in stage I and II disease, and regimens with curative intent in stage IIIa and IIIb discasc. Future directions for vinorclbine in the treatment of NSCLC *re likely to bc dire&d toward combination trials with other agents active in NSCLC. Cumnt phase I-U trials, for example, combine vinorclbinc with cisplatin, 5-fluorouracil/ Icucovorin, mitomycinC, ifosfamidc, carboplatin, and paclitic (Taxol; Bristol- Myers Squibb Co, Princeton, NJ). Some pbasc III trials *rc planned and some arc under way. Vinorclbinc has been * focus of intcrcst in multimodality trials. A Canadian trial, for example, combined vinorclbine and cisplstin, followed by accelcmted radiation. Results fmm all these trials can be expected to guide the further development of vinorclbinc in adjuvant and neadjuvant settings in. NSCLC. Moreover, trials that *rc documenting the cficacy of vinorclbine in small cell lung cancer arc just beginning.

ApbrseIIstudyofeisplrtio,5nuormr~e~~dlaKovorinaug-meoted by viaorelbinc (Navelbiae) for advanced non-small cell lung cancer: Ratim~de md study desi@ kkcs EE, Drinkard LC, Samucls BL, Hoffman PC, Watson S, Bitran JD et al. Universiry o/Chicago, 5841 SMmyland Ave. Chicago, IL 60637-1470. Scmin oncol 1994;21:Suppl, 10:79&t

In a randomized phase IJ study by the Cancer and Leukemia Group Et, the cispl*tin/5-fluomuril/leucovorin (F’FL) combination produced II 29% response rate in advanced, unresectablc non-small cell lung cancer. Vinorelbine (Navelbinc; Burroughs Wellcome, Co, Research Triangle Park, NC; F’icrm Fabre Medicamcnt, Paris, France), * scmisynthetic vinca alkaloid, has also demonstrated single-agent activity in this disease. Therefore, * phase I-II study was designed to investigstc the addition of vinorelbinc in cecalating doses to the PFL combination. The objectives of this study were to establish the maximum tolerated dose of vinorclbinc in combination with PFL, and to define the overall response rate in * cohort ofpatients treated with the maximum tolerated dose. The regimen consisted of vinorelbine in escalating doses starting at 20 mg/m’/d intmvenously on days 1 and 5, followed by leucovorin 100 mg orally every 4 hours on days I to 5, 5- fluoroumcil800 mg/m*/d intravenous continuous infusion days 2 to 5 (96 hours), snd cisplatin 100 mp/ml intravenously 12 to 24 hours after administration of the first dose of vinorclbine. Cycles wcrc repeated every 3 weeks. No dose- limiting toxicity w*s observed in the first five patients treated with the initial vinorelbine dose. Increasing the dose of vinorelbinc to 25 mplrnl in * second cohort of two patients, however, resulted in gmdc 4 granulocytopcnia in both, and grade 4 diarrbes in one. It was concluded that this dose level w*s not feasible. During * preliminary analysis, one complete rcsponsc and three partial responses were obscrvcd in 16 patients evaluated, one of these patients had *pathologic complete remission. This early analysis indicates activity for the regimen.

Vinorelbine (Navelbine)/carboplatin combination therapy: Dose intensif~ation witb granulacyte cdony-stimulating factor Crawford J, O’Rourkc MA, Coltman CA Jr. Deporbnenr o/Medicine, Duke Universily Medical Cenle: Box 3198. Durham. NC 27710. Scmin Oncol 1994;21:Suppl 10~73-8.

Treatment with platinum agents or the new vinca elkaloid vinorclbine @*velbinc; Burroughs Wellcome Co, Rcscarch Triangle Park, NC; Pierre Fabre Mcdicamcnt, Paris, France) results in prolonged survival in patients with advanced non-small ccl1 lung cancer (NSCLC). To dctrrmine whether * unique combination of these *gents might enhance activity against NSCLC, * combination chemotherapy regimen consisting of intravenous carboplatin, administered on days I and 29, and intravenous vinorelbine, given once weekly, w*s evaluated. Because the dose-limiting toxicity of both agents is myelosupprcssion, an additional study goal WBS to assess the ability of granulocytc colony-stimulating factor to alleviate hcmatologic toxicity and allow on-time, fulldose vinorclbine therapy. To this end, * phav I/II study WBS begun. Phase I of the study included 22 patients (15 men end scvcn women) with * median age of 63 yeers (age range, 39 to 77 years) who had stage lV NSCLC and no prior chemotherapy. Phase I consisted of28day cycles in which intravenous csrboplatin wss administered at *n area under the curve of 7 by the Calvcrt formula. dose range 350 to 450 n&n’, and intravenous vinorelbinc was administered weekly. Granulocyte colony-stimulating factor w*s administered if dose-limiting neutropcnia developed. Four cohorts of patients wcrc studied, ranging from those who received no vinorelbinc to those who rcceivcd drug doses of up to 30 mg/m*. Patients were able to tolerate the highest dose of vinorelbine, but the majority required gmnulocyte colony-stimulating factor support to do so. No novel toxicities wcrc observed in patients treated with the combinatmn of carboplatin snd vinorclbine. Both the response rate (29% in patients treated with both agents) and preliminary survivsl data suggest that this regimen holds promise for the treatment of patients with NSCLC.

Viiodbii (Navelbioe) in tbe adjwant aod q eoadjuvant treatment of non-small cell lung cancer Vwdlet J, Ayoub J, Rousseau P, Souhami L, Hohneker J, Shepherd F. Deparbnenr of Oncology, Monbvol General Hospital, I650 Cedar Ave. Montreal. Que. H3G IA4. Scmin Oncol 1994;2l:Suppl 1064-72.

Several Canadian centers arc studying the favorable activity and toxicity profile of vinorclbinc (Navelbinc; Burroughs Wcllcomc Co. Research Triangle