407

Randomized Study Comparing Cisplatin(CDDP) and Vindesine(VDS) Combination(PV) and CDDP. VDS and Ifosfamide(IFX) Combinatibn(PV1) in- Non-small Cell Lung Cancer(NSCLC)

Shunkichi HIRAKI, Taisuke OHNOSHI, Hiroshi UEOKA, Takashi HORIGUCHI, Tsuyoshi KODANI and Ikuro KIMURA Department of Medicine, Okayama University Medical School, Okayama 700, Japan

Based on the results of a pilot study assessing the effect and toxicity of PVI in advanced NSCLC, we activated a randomized study comparing PV and PVI in December 1987. A total of 89 patients has been randomly allocated to receive either PV or PVI. PV consisted of CDDP 20mg/m2, on days 1 to 5; VDS 3mg/m2, on days 1 and 8; repeating q.4wks. PVI consisted of CDDP 20mg/m2, on days 1 to 5; VDS 3mg/m2, on days 1 and 8; and IFX 1.3g/m2, on days 1 to 5; repeating q.bks. A total of 83 patients was fully evaluated for tumor response and toxicity, so far. Results were the followings:

PV PVI III IV III IV

No. evaluated 18 22 19 24 No. responding(%) lO(56) MST(months)

4(18) 13(68) ll(46) 9.0 9.3

1-yr surv. rate(%) 40 38 Myelosuppression was the major toxicity for both arms, but it was more frequent and profound in PVI than in PV. AS a tentative conclusion, there appears to be no advantage, of additional IFX to PV in terms of patient survival.

409

A PROSPECTIVE STUDY OF LOW DOSE ORAL mOPOSlDE IN POOR PROGNOSIS SMALL CELL

LUNG CANCER (SCLC). A J Forward for the West of Scotland Lung Cancer Group Low dose oral etoposide has been advocated as a palliative regime for advanced SCLC. 27 patients with symptomatic poor prognosis SCLC were entered into a study of 4 courses of oral etoposide (5Omg twice daily) for 14 days, repeated at day 22. 17 patients (12 male) between 51 and 77 years (median 66) are currently evaluable. 7 patients were unable to finish the first course and only 6 patients were able to complete all 4 courses. At 12 weeks 3 patients had a CR radiologically, 3 had PR, 6 had progressed and 5 had died, 2 of drug toxicity. Nausea was mild but often persistent, 1 patient had recurrent bronchitis and one required multiple transfusions. Symptomatically in responders there was a mild improvement in cough and haemoptysis, but not in pain relief or nausea. ITOG performance status and dyspnoea grade also improved slightly in the 6 patients who responded. In our patients with poor prognosis only 35% were able to complete the 4 courses of treatment. It provided poor palliation of disease, gave poor response rates, with relatively high toxicity.

111

408

LONG TERM ~URWVU ANALYSIS OF STADE 111 & iv NON- SMALL CELLbJNDCANCER PATIENTS (Ro)hEAlEDWlTH EMTREXATE (ETX, lo-EDAM).MG Kris, RJ Grab, LM

Potanovid~, LD Marks, KMW Pisters, TA Terzakis, RT Heelan. Memorial Sloan-Kettering Cancer Center New York, NY & Ciba- Geigy Inc., Summit, NJ, USA

ElX has greater preclinical antitumor activHy and more selectiie entry into neoplastic cells than other antifolates. In consecutive trials, 119 pts untreated with chemotherapy received outpatient El’X alone or with mitomycin (M) and vinblastlne (V). Thii report reviews mature data from studies completing enroi- lment by l/90. ETX(4fMO mg/m2) was given weekly x5 then every other week. Combination chemotherapy pts received V on the same schedule: 4mg/m2 dl, 2mg/m* d8, 4.5 mg/m* thereafter. M (ems/m’) was given day 1,29 & 71. R characteristics: stage IIIA - 7%, IllB -33%, IV - 60%; men 85%; KPS 80+90% - 58%, KPS 50- 70% - 42%; wl bssz8% - 33%; t serum LDH - 40%; adenoca - 81%, epidermoid - 23%; median age 59 yrs. Response data:

!!! SW IMedl 1 Yr Surv El-x 20

2 Rate 10.8 mo 45%

ETx+WJ 99 59% 14.5 mo 58% In the ETX+MV trial, symptoms of cough, dyspnea, pain & hemoptysis significantly improved. KPS was stable or better in 82%; 82% gained wt. Leukopenia & mucositis were the most common adverse effects. In conclusion: 1) ElX is active alone & in combination with MV in NSCLC pts previously untreated with chemotherapy. 2) Median survival for pts receiving ElX+W exceeds 1 yr. 3) EfX improves lung cancer symptoms and results in weight gain. 4) Randomized trials of ElX+W regimens are in progress. Supported by Ciba-Geigy, Inc. and CA-05828.

410

PHASE II TRIAL OF HIGH DOSE EPIRDBICIN AND IFOSFAMIDE IN ADVANCED NON SMALL CELL LUNG CANCER(NSCLC).

F.De Marinis,F.Nunziati,M.A.Noseda,M. Signora,l4.R.Migliorino,M.Vaccarino and G.Pallotta 61 F.Salvati.Y.Forlanini" Hospital-3rd/8th Pneumological Divisions, Rome-Italy.

From June 1989 to Warch 1990,25 untrea- ted pts entered in a phase II study with Epirubicin(100mg/mq,d.1),Ifosfamide(2.5g/mq, d.l-2) and Mesna(20% of IF0 dose,tiae 0,4,8 h)every 28 days.24 male were treated, 16 squamous,9 adeno,l3 IIIB and 11 IV stage. Median age was 63 and PS O-l (ECOG). After 2 cycles 24 Dts were dvalu&le(l early death):8 PR(33.5%),10 NR (41.6%),6 P(25?.),documented by TC and FRS. Toxicity:myelosuppression was the most important toxicity(23.5% of leukopenia of WHO grade III-IV,4% of anemia of grade III- 1V);we observed 2 episodes of renal toxicity of grade II,2 of cardiac toxicity of grade II.The 12 months survival percentage has been of 24%.The median survival has been of 7.4 mo for entire group:10 mo for responders vs 6.2 mo for non-responsers(p=NS).We conclude that, in spite of 45% of stase IV.we obtained a good response(33.3& -of Pk),and we hope that the addition of CSF's,will surely reduce myelosuppression, dose-limiting toxicity.