III

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RESULTS OF A PHASE II STUDY WITH VINORELBINE (VNB) IN PATIENTS WITH ADVANCED NON SMALL CELL LUNG CANCER (NSCLC). M. Rinaldi, M. Della Giulia, T. Gionfra, I. Venturo, A. Casali, M. Rosselli, G. Paoletti, M. Lopez. Oncologia Medica II, Istituto Regina Elena, Roma, Italy.

VNB is a unique, semisynthetic vinca alkaloid showing activity in NSCLC. To evaluate the feasibility and the efficacy of VNB in pretreated’patients with NSCLC we started a study with this drug at the dosage of 20 mg/m* once a week with a rest of a week every two, till progression or unacceptable toxicity. 16 patients entered the study: 2 have been previously treated with carboplatin and etoposide, 14 with cisplatin and etoposide and all were progressed during thera- PY.

Patient median age was 69 (range 36-78). Eighteen patients had souamous carcinoma. 4 undifferentiated. 4 adenocarcinoma. Median number of courses was 6 (range 2-20).

No responses were obtained, 8 patients were NC, 4 PD and 4 were not evaluable (2 for early progression, 1 lost, 1 for early neuro- toxicity). Median time to progression was 115 days (range 56-190). No G4 toxicities were noted neither in bone marrow parameters or in neurological signs.

Second line chemotherapy with VNB is not active in advanced NSCLC at least at the dosage used.

Since no additive toxicity with previous chemotherapy was obser- ved, it is reasonable to test the drug at higher dosages in an effort to obtain objective responses in this dismore patient population.

Six naive patients older than 70 years or not susceptible of more aggressive chemotherapy were treated with the same schedule: 2 PR were obtained. As first line chemotherapy, no conclusions can be drown? but 2/6 responses seems to confirm the VNB effectiveness in this disease and its use may be suggested at least in this specific subgroup of patients.

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A PHASE II STUDY OF LOW DOSE VINORELBINE IN PATIENTS WITH ADVANCED NON-SMALL-CELL LUNG CANCER (NSCLC). K. Gyi, R. Milroy and S Banham’, Departments of Respiratory Medicine, Stobhill Hospital and ‘Royal Infirmary, Glasgow, Scotland, U.K.

Intravenous vinorelbine (30mg/m*, weekly) has been used in the palliation of NSCLC (Seminars in Oncology 16 supp 4,26, 1989). An objective response rate of 33% has been reported but this was associated with significant haematological toxicity (neutropema in 49% of cycles and anaemia in 42% of cycles). We used low dose vmorelbine (25mg/ms, weekly) to see if similar activity could be achieved with less haematological toxicity.

Nine patients with previously untreated Stage III NSCLC were studied. The median age was 67 years (range 60-75 years) and all were of ECOG performance status 1 and 2. A total of 67 cycles were given (median 8, range4-12).

Five of nine patients showed a minor response but there were no objective responses. The median duration of the minor responses was 26 weeks (range 14-38 weeks). Of the 9 patients 3 are still alive. The median survival of the 6 others was 33 weeks (range 16-78 weeks).

This dose was well tolerated with grade 112 neutropenia in only 29% of cycles and mtld anaemia in only 22%. Minor constipation was seen in 5 patients and grade 1 alopecia was seen in 4. No sigmficant sepsis or neurological toxicity was seen.

This dose of vinorelbine has limited activity in NSCLC. It is well tolerated with no significant haematological toxicity. Further studies using vinorelbine in combination with other cytotoxic drugs in the treatment of NSCLC are planned.

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PHASE II TRIAL OF ORAL UFT AND CISPLATIN IN NON-SMALL CELL LUNG CANCER. Y. Ichinose, H. Asoh, T. Yaw H. Yokoyama, T. Inoue, N. Takanashi, N. Hara*, M. Ohta. NatIonal Kyushu Cancer Center, "Kyushu University, Fukuoka. Japan. UFT. a combination of uracil and the 5 fluorouracil (5-FU)

analogue, 1-(Z-tetrahydrofuryl)-5-fluorouracil, is shown to enhance antl-tumor activity as compared to WU alone. In addition, the combination of 5-FU and cisplatln has proved to have a synergistic anti-tumor effect. For this reason, we conducted the phase II trial of the combination chemotherapy using UFT (400mg/m2, p.o.. days l-21) and cisplatln (80mg/m2, 1.v.. day 8) every 4 weeks for treatment of non-small cell lung cancer (NSCLC). Between Z/92 and 11/93, 31 patients with inoperable NSCLC were entered into this trial. They were all considered eligible: mean age 61 (36-75); male/female. 23/8: stage III/IV, 12117; PS O-1/2, 2714: prior therapy/no therapy, 7124. As of Nov. 1993, 30 and 29 patTents were evaluable for treatment toxicity and response, respectively. Median number of treatment cycles was 2 (l-4). Hematologlc toxlclties. lncludlng neutropenia or thrombocytopenia with grades 3 and 4, occurred in only 7%. Non-hematologlc toxicities with grade 3 were nausea & vomltlng (17%). anorexia (7%) and renal dysfunction (3%). There were 10 partial responses (35%; 95% confidence limits 17-52%). These observations suggest that cisplatln plus oral UFT 1s a well tolerated regimen with modest activity in NSCLC and that It should be possible to combine another active agent with this regimen.