106 High-dose therapy with etoposide, ifosfamide, carboplatin, and epirubicin (VIC-E) in non-small cell lung cancer (NSCLC)

30 (7.1%) leukocytopenia (5.7%), nausea/vomiting (4.3%) stomatitis (4.3%), and diarrhea (4.3%). Median survival time of enrolled pts was 263 days, and median survival time by stage was 310 days for IIIA, 354 days for 1118, and 205 days for IV. In view of the efficacy and toxicity of Emitefur, combination therapy with other anticancer agent(s) is warranted.

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105

Peripheral chemotherapy

D.J. Dunlop, Haematology UK

blood

stem cell (PSSC) support for in small cell lung cancer (SCLC)

E.J. Fitzsimons. Deprs of Medical Oncology and Glasgow Royal infirmary and Western Infirmary,

ICE

Glasgow,

Introduction: PBSCs are known to accelerate engraftment following high dose chemotherapy but less information is available in relation to PBSC support for conventional chemotherapy. Recently reinfusions of whole blood containing haemopoietic progenitors have been used with G-CSF to support and accelerate ICE chemotherapy in SCLC, (J Clin Oncol 13: 148-156, 1995). The aim of this study was to assess the ability of haemopoietic progenitors obtained by leucopheresis to support ICE chemotherapy. Methods: In a prospective pilot study, patients with SCLC received ICE chemotherapy, (Ifosfamide 3 g/m2, carboplatin 400 mgfm’, etoposide 700 mg/m*), 3 weekly. G-CSF (Granocyte, Chugai Ltd,) was administered at a dose of 260 &day on days 7-14 during cycles 2 and 3 prior to leucopheresis. Aliqouts of PBSCs > 1 .O x lo6 CD34 cells/kg, (mean 2.11 x lOa CD34 cells/kg), were reinfused 48 hours after chemotherapy treatments 4, 5 & 6. Comparison of myelosuppression kinetics in unsupported cycles was made with G-CSF supported, (cycles 2 and 3) and PBSC supported cycles, (cycles 4, 5 and 6). Results: 13 of 18 enrolled patients were evaluable in the study. Data was pooled from all control cycles, and compared to pooled data from G-CSF and from PBSC supported cycles using paired t-Tests. Mean neutrophil nadirs in G-CSF supported cycles were significantly improved compared with unsupported or PBSC supported cycles, (p = 0.0006). The mean day of achieving a neutrophil count of 0.5 x log/l in G-CSF supported cycles, was significantly earlier compared with unsupported or PBSC supported cycles, (p = 0.0009). A dose of greater than 1.5 x lo6 CD34 cells/kg significantly improved thrombocytopenia in later cycles. With this dose of PBSC support significantly fewer treatment cycles, (2/20 compared with 15/30) were complicated by thrombocytopenia of ~50 x log/l, (Chi-* test 0.002). Conclusions: This small study suggests that G-CSF is superior to PBSC in supporting chemotherapy induced neutropenia with ICE chemotherapy. Cumulative thrombocytopenia complicating ICE chemotherapy is improved with PBSC reinfusions above 1.5 x lo6 CD34 cells/kg.

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106

High-dose therapy with etoposide, carboplatin. and epirubicin (VICE) lung cancer (NSCLC) .

ifosfamide, in non-small

cell

’

S. Fetscher, W. Brugger, R. Engelhardt, L. Kanz, J. Hasse, H. Frommhold, M. Wenger, R. Mertelsmann, W. Lange. University of Freiburg Medical Centre, Germany We report a phase l/II trial to assess the feasibility and activity of chemotherapy with etoposide, ifosfamide, cisplatin, and epirubicin in limited-stage (LS, stage I-;lllB) and extensive-stage (ES, stage IV) non-small-cell lung cancer (NSCLC). Chemotherapy followed by granulocyte colony-stimulating factor was given at a dose of etoposide (500 mg/m*), ifosfamide (4000 mg/ma), cisplatin (50 mg/m*), and epirubicin (50 mg/ma) (VIP-E) to 107 patients with NSCLC. 25 patients proceeded to high-dose chemotherapy with autologous peripheral blood stem cell transplantation after etoposide (1.500 mg/m*), ifosfamide (12.000 mg/ma), carboplatin (750 mg/m*) and epirubicin (150 mg/m’) (VICE) condrtionmg. Results of conventional-dose VIP-E: 35/102 (34%) patients responded (2 CR, 33 PR), 33/102 (33%) showed no change (NC); the remainder progressed with therapy (PD). Objective response rate was 68% (4% CR, 64% PR) in LS-NSCLC and 22% (1% CR, 21% PR) in ES-NSCLC. Median duration of survival was 13 months in LS-NSCLC and 5.5 months in ES-NSCLC. P-year survival was 26% in LS and 2% in ES-NSCLC.

Results of high-dose VICE: 23/24 evaluable patients improved or maintained prior responses (92%) 1 patient showed NC. Treatment mortality was 4%. Median duration of survival was 17 months in LS-NSCLC and 10 months in ES-NSCLC. 2-year survival was 30% in LS and 8% in ES-NSCLC. Conclusion: Response-rates and survival after VIP-E are comparable to published trials of chemotherapy in NSCLC. Toxicity is acceptable in LS, but unacceptable in ES-NSCLC. Better response-rates achieved in the high-dose arm did not translate into improved survival. ES-NSCLC patients do not benefit from VIP-E conventional dose, or from VICE high dose chemotherapy. Whether selected LS-patients with good responses to VIP-E could benefit from adjuvant or neo-adjuvant dose intensification remains to be determined. Additional results based on further follow-up data and additional patients will be presented.

Thursday, 14 August 1997 POSTER

SESSION

Chemotherapy 11071

Dose finding study previously untreated

of paclitaxel non small

and carboplatin cell lung cancer

in

G.V. Scagliotti ‘, L. Crinb”, P. Masiero’, M. Palladinoa, A. Mattei ‘, A. Gentile 3, M. Tonato 2. ’ University of Turin, Department of Clinical & Sio/ogica/ Sciences; p Medical Oncology Policlinico Monteluce, Perugia; 3Brisfo/ Myers Squibb, Rome, #a/y Fifty previously untreated patients with metastatic or locally advanced Non-Small Cell Lung Cancer (NSCLC) were enrolled in a phase I trial of combined Carboplatin and Paclitaxel, the latter administered as 3-hour infusion after standard premeditation for hypersensitivity reactions, Paclitaxel starting dose was 130 mg/ma, to be escalated by 10 ms/ma increment for each triplet of enrolled patients, to a maximum dose of 235 mg/m*. Carboplatin doses, administered as l-hour infusion, were increased of 2&30 mg/m* for each triplet to a maximum dose of 375 mg/m’. Patient characteristics include a median age of 57 years (range 38-73) and an ECOG Performance Status of 0 (25 patients), 1 (20) or2 (5). Histological subtypes were 21 squamous cell carcinomas, 19 adenocarcinomas, 2 large cell carcinomas and 8 unclassified NSCLC. Thirty-one patients were clinically staged as Illb, one as llla and 18 as stage IV. One hundred and seventy cycles of chemotherapy were administered (median number of cycles for patient = 4, range 1-8) and the dose-limiting toxicity for the combination was reached at Carboplatin 375 mg/m* and Paclitaxel 235 mg/m’ mainly comprised of acute and subacute neuromuscular pain. Other non hematological toxicities were negligible. Hematological toxicity was independent by Carboplatin and Taxol dose and mainly comprised of neutropenia (grades Ill and IV in 11% of the cycles, IO patients) whilst piastrinopenia grade Ill was reported in only 2 patients. Globally 14 partial responses and 1 complete response (32%) 22 stable diseases and 9 progressive diseases were documented in 45 evaluable patients. Objective responses were documented both in stage lllb and IV. Four patients initially staged as lllb were converted to surgery after chemotherapy The suggested doses for a phase II study are Carboplatin 375 mg/ma and Taxol 225 mg/m’

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108

Paclitaxel (TAX) and carboplatin (CP): A phase study in advanced non-small cell lung cancer patients (PTS)

I

A. Paccagnella, A. Favaretto, G. Di Vittorio’ , F. Oniga, L. Ossana. Medical Oncology De@; ’ Pneumonology De@, Azienda Ospedaliera, Padova, ha/y TAX has significant activity in NSCLC. CP has less non-haematologic toxicity but comparable activity to Cisplatin. The optimal dose of CP and TAX has not yet been determined. The CP starting dose was 175 mg/m2, with increments of 25 mg/m2. The fixed TAX dose was 175 mg/m2. The