102

386

SMALL CELL LUNG CANCER (SCLC) : A RANDOMIZED CLINICAL TRIAL OF CYTOXAN, DOXORUBICIN- ETOPOSIDE (CDE) vs CISPLATIN-CDE (P-CDE). B. Lebeau*, Cl. Chastang, F.X. Lebas, Ph. Delaval, F. Boita, F. Blanchon, M. Momet, G. Adam, G. Desrivot, E. Bouchaert and the “Petites Cellules” Group. *Hbpital St Antoine, 7.5012 Paris, France.

In May 1988, the “Petites Cellules” group started a trial assessing the addition of CisPlatin to a classical CDE chemotherapy in SCLC patients. Patients were randomized to receive either every four weeks CDE (Cytoxan 1 g/m2 N dl, Doxorubicin 45 mg!m’ N dl, Etoposide 150 mg/m2 N dl-2) or P-CDE chemotherapy (CDE t Cis-Platin 100 mg/m” N dl). Patients accrual ended at March, lst, 1993, when 459 pts entered the trial, including only 97 pts (21 %) with limited forms, as our group managed a competing trial that aimed at assessing thoracic radiotherapy in limited disease. The results are summarized in the table :

Responsenot Median Number CR PR NR evaluable survival Toxic

of pts (%) (a) (%) ( ) % (days) deaths CDE 228 16 37 40 7 267 13

P-CDE 231 30 43 11 17 27.5 29

In these poor prognosis patients, P-CDE significantly increased objective response @ < O.OOOl), but no survival benefit was observed @ = 0.63,2 sided logmnk test). One explanation could be the higher rate of toxic deaths observed in P-CDE group (p = 0.014, Fisher’s test). CSF were not used in this protocol ; its prescription could reduce the rate of deaths due to bone marrow hypoplasia in future trials.

388

CISPLATIN (DDP) 5 FLUOROURACIL (5FU) INDUCTION CHEMV FOR CERERRAL METASL4SE5 FROM SMALL CELL LUNG CANCER (SCLC). J.F. Morere, L. Israel, F. Tcherakian, C. Boa& A. Duran, J.P. Bat&&I, J.L. Breau. Cliique d’Oncologie M&&ale, H6pital Avicenne, Bobigny, France. 26 patients (22 men and 3 woman) with cerebral metastases from SCLC received an hrductlon DDP-SFU chemotherapy. In 20/26 cases, cerebral m&stases ware present initially and in 2126 cases they occurred at a later stage. All ware diagnosed on the findings of a contrast enhanced CT-scan, performed systematically in 18 of the 20 cases affected initially and in 8 cases assoelated with neumlogical problems. In 9 cases the cerebral metasmses were single and in 17 cases, multiple. DDP 20 mg/mWay and 5FU 600 mg/m’/day were given in an extended intravenous infusion, from day 1 to day 5. A median number of 2 courses of treatment were given (range l-7). Response was assessed by neurological examination and contrast enhanced CT-scan. 10 complete responses and 12 partial responses could be achieved. The overall response rata is 84 % (wntidenca interval 72 96 - 98 %). The chemosensitivity of 18 of the 20 initial metastases group was similar to that of metastases in other tumour sites. Toxicity was mainly of a hematological nature, with 926 patients having, thrombocytopenia (grade 2, 3 and grade 3, 2) and 3R6 having leucopenia (grade 2-3). Later 22/26 received systematic consolidating radiotherapy and 3 received it on relapse. Cerebral recurrence occurred in 10 of the 20 initial metastases group and in 4 of the 6 late metastases group. The median disease free for the initial metastases group is 9 months (range from 2 to 24 months). In 9 cases cerebral recurrence was implicated in the death of the patients. Systemic induction chemotherapy DDP-SFU is effective for palliation of brain metastases. ‘The usefulness of thii combination associated with consolidating radiotherapy should be assessed in a randomized trial.

387

A RANDOMISED TRIAL OF 4 VERSUS 8 COURSES OF CHEMOTHERAPY WITH IFOSFAMIDE , EPIRURICIN AND ETOPOSIDE (EVI) IN EXTENSIVE SMALL CELL LUNG CANCER (SCLC). OJARRY, P.FOIJRNEL, for the Groupe Lyonnais d’Oncologie Thoracique. Departement of Thoracic Oncology. (GLOT) - Pr.BERNARD, C.H.Lyon Sud, 69310 PIERRE BENITE.

Objectives of the study were to assess if median survival time, free disease swvival and long wvivors can be improved by maintensace chemotherapy in patients (pts) with extensive SCLC. Extensive disease was detined as follows : involvement of sus-clavicular or peripheral lymph nodes (43 pts), pleural et&ion (22), contra-lateral lung(l) or metastaxs @one 54, liver 41, CNS 34, bone marrow 33, adrenal 20 , pericardum 5). Since 06 1989 to 03 1993 , 122 pts (median age 56 yr) with extensive SCLC were enrolled in a prospective random&d trial ; all were supposed to receive 4 courses of Ifostknide Iglm* iv D I and 2, Etoposide 150 mp/m’ iv Dl and 2 and Epirobicin 50 ms/m’ iv D2 (EVI) at 3 weekly intervals, and then responders were randomly allocated to receive either 4 more course EVI (maintenance arm M) or no forther chemotherapy (non maintenance arm NOM). Retreatment was allowed in each arm when progression. The median follow-up is 29 months (Range 10-45) Thirty two patients were randomised in (M) arm and 33 in (NOM) arm, while 57 were excluded for”no change”, progression or death (response rate = 56,5 % , CR = 7,3 %, PR = 46 % and MR= 3.2 %).The M and NOM arms were comparable for all but Kamofsky index (21 patients >= 80 % in NOM versus 12 in M arm)

We didn’t find any difference between the 2 amu for median survival time : 9 months in NOM vs 7,7 in M @=0,93 Log P.ank test), free disease sowival or long survivors.Toxicity was low with only one toxic death, and 35 patients (28,6 %) experienced febrile aplasia and among randomised patients only 18 experienced lie-threatening (WHO IIl or IV) haematologic toxicity in the induction chemotherapy, while only 3 in M arm. Thos we conclude that EVI is an effective chemotherapy with acceptable toxicity and maintenance chemotherapy doesn’t improve sorvival in extensive SCLC of retreatment when progression if performed.

389

SWOG 8609 -A PHASE II TRIAL OF TENIPOSIDE (VM-26) AS THERAPY FOR EXTENSIVE SMALL CELL LUNG CANCER (SCLC). V. Canfield, P. Grozea, J. Crowley, and R. Livingston Oklahoma City, OK and Seattle, WA.

Because of promising results reported by Bork et. al (J. Clin Oncol 4:524-27, 1986) the Southwest Oncology Group conducted a phase II trial of VM-26 in patients (pts) wsh extensive SCLC.

Between 9188 and 1 i/90 41 eligible pts with extensive SCLC were enrolled on a phase II trial of VM-28; 80 rn@m’ IV days l-5 every 21 days. This schedule was identical to the Danish regimen. No patient had received prior chemotherapy or radiotherapy and all had a PS of 2 or better (O-l, 24 pts; l-2, 17 pts). 28 males and 13 females were evaluable. The median age was 84 (range 46-83).

Pts were assessed for response after every cycle of therapy and therapy discontinued with disease progression or stable disease after three cycles. Doses were adjusted for day 1 or nadir leukopenia or thrombocy-topenia or any grade Ill non-hematologic toxicky.

15 pts (37%) developed grade 4 leukopenia or granulocytopenia and 1 died of respiratory infectlln. 1 pt had grade 4 hyponatremia. Other toxicities (grade 1-3) included anemia (24) nausea (20), thrombocytopenia (lo), vomiting (9), infection (7) alopecia (4). diarrhea (4). hypotension (3) LFT rise (3) skin rash (2) weakness (2) weight loss (2) hypertension (2) anorexia (2). elevated creatinine (2) malaise (1) edema (I), elythema (1) stomatitis (1) MS changes (1). Most toxicities were grade 1 or 2.

The overall response rate was 24% (95% Cl 12% - 40%). There was 1 complete response and 9 partial responses. Median survival was 7 months.

This trial failed to confirm the response rate of 90% reported by Bork et. al. Results similar to our trial have been reported by MD Anderson Cancer Institute (Holoye et al., Proc. ASCO, Vol 8. p 243, 1989). Survival rates in our trial and the Danish trial were similar.

It remains unclear whether VM-28 has any advantage over VP-18 for treatment of extensive small cell lung cancer. At the dose and schedule used by SWOG VM-28 had only modest activity.