119

red in 18 patients and there was 3 toxic deaths. Mucositis was common after metho-

trexate but was seldom severe. The primary site was the initial site of relapse in 50% of patients. In 16 LD/CR patients given radiotherapy only 5 out of 12 relapsed at the primary site. In i0 LD/CR patients not given radiotherapy 8 out of 8 have relapsed at the primary site. These results indicate that short duration intensive chemotherapy with moderate toxicity can result in excellent response rates. Al- though median survival may be slightly shorter than in some studies there is sub- stantial potential for long-term survival.

Non Small Cell Lung Cancer: A Randomised Comparison of Chemotherapy With No Chemo- therapy. Woods, R.L., Levi, J.A., Page, J., Raghaven, D., Fox, R., Tattersall, M., Stuart-Harris, R., Byrne, M. Royal North Shore Hospital Sydney, Australia.

115 evaluable patients (92M,23F) aged 30-79 yrs (med 58) with inoperable non small cell lung cancer were randomised to 9 receive chemotherapy (cis platin 120 9g/m- i.v. four weekly and vindesine 3 mg/m- i.v. weekly) (CT) or no chemotherapy (no CT). Two courses were given prior to full reas- sessment. Patients showing signs of response continued chemotherapy for 6 courses or until tumour progression occurred. There were 45 squamous cell carcinomas, 44 adeno- carcinomas and 26 large cell carcinomas. Performance status (ECOG grades) included 29 (25%) grade 0, 58 (51%) grade i, 20 (17%) grade 2, and 8 (7%) grade 3. 3~ pa- tients (30%) had limited but inoperable disease. 20 (17%) had lymphadenopathy and 61 (53%) distant metastases. 38 patients (33%) had received prior radiotherapy (RT). 56 patients were randomized to CT and 59 to no CT. There was no imbalance according to age, sex, histopathology, PS, prior RT or extent or sites of tumour in the two groups.

Toxicity (WHO criteria) was severe in those patients receiving CT with virtually all patients having severe nausea and vomi- ting, 29 (52%) grade 3 or 4 myelotoxicity, 7 (13%) grade 3 or 4 nephrotoxicity and 18 (30%) mild to moderate neurotoxicity. 18 patients (32%) responded by standard criteria, including 3 complete responders and 15 partial responders. 70 (61%) patients have died. The overall median survival time (MST) was 20 weeks. MST was 20.5 weeks for CT patients and 16 weeks for no CT patients; for responders the MST was 24 weeks and non-responders 19 weeks. Log rank analysis showed no significant dif- ference in survival by treatment given. Chemotherapy with cis platin and vindesine

in these doses induces a significant num-

ber of responses but does not have a major im- pact on survival of patients with non small cell lung cancer.

An Analysis of 134 Phase II Trials in Non-Small Cell Lung Cancer (NSCLC). Kris, M., Cohen, E., Gralla, R. Memorial Sloan- Kettering Cancer Center, New York NY, 10021, U.S.A.

We reviewed 134 phase II single agent trials enlisting 4340 patients (pts) with NSCLC from 1970-1983, to: i) evaluate response rates, 2) examine pt and study parameters, and 3) deter- mine if this review could aid planning of fu- ture trials. Sources for this analysis included a computerized manuscript search and an Index Medicus review. Of 51 agents studied, 42 were tested in > 14 pts. Of these 42 drugs, only 5 had major activity > 15%: cisplatin (16%/305 pts) , ifosfamide (27%/130 pts) , mitomycin (17%/88 pts) , vindesine (18%/370 pts), vinblastine (18%/22 pts). The frequencies of reporting of pt characteri- stics were: age-66%, prior treatment status- 65%, performance status-58%, weight loss-4%. Only 51% of agents were tested at more than one center; 65% of trials included > 19 pts. Response rates did not vary by NSCLC histologic type (epidermoid ca and adenocarcinoma both 11%; large cell 9%), either overall or for each of the 5 active agents. In 41 of the 134 trials, a 0% major response rate was seen. In 18 of these "negative trials", < 15 pts were entered and in 14, > 20 pts were treated. Although ra- tes were higher in previously untreated pts overall (13% vs 4%), all active agents so stu- died had responses in pts with and without pri- or chemotherapy. We conclude: I) only 5 of 42 drugs studied in 14 or more pts had activity > 15%; 2) pt characteristics of prognostic im- portance are often lacking; 3) many agents have been tested in an inadequate number of pts and/or trials; 4) response rates do not differ by NSCLC histologic type; 5) too often "negati- ve trials" do not include enough pts, or stu- dies are continued after conclusive negative results have been obtained; and 6) studies can reasonably include both previously treated and untreated pts. Supported by Ca-05826 and the Tishberg Fund.

Chemotherapy of Metastatic Non-Small Cell Lung Cancer (NSCLC): The Eastern Cooperative Oncolo- gy Group Experience. Ruckdeschel, J.C., Finkelstein, D.M., Ettinger, D.S. Albany, Boston and Baltimore, United

States. Between 1981 and 1983 the ECOG compared the

4 most active regimens for metastatic NSCLC in a prospectively randomized study. The majo- rity of patients were fully ambulatory (PS 0,i; 81%); male (70%); and had no prior surgery (79%) or radiation (62%). Patients with ipsi- lateral mediastinal metastases only were con- sidered regional disease and excluded. Each of

the regimens was given exactly as described

1 2 0

in initial reports and was tested in all 3 subtypes of NSCLC: squamous, large cell ana-

plastic and adenocarcinoma. Results were as follows :

Reg~Lmen* #pts CR PR (CR+PR)Z Median Jdrug S u r v i v a l deaths

H I - V - P 121 6 31 31 22 w 7 C-A-M-P 115 1 19 17 25.l v 0 £-p 126 6 26 25 26 w .V-p 12& 2 23 20 26.6 w 5

*A=doxorubicin, C=cyclophosphamide, E=eto- poside, M=methotrexate, Mi=mitomycin, P= cisplatin, Pr=procarbazine, V=vinblastine, Vd=vindesine. Although the response rate of MiVP was higher there was no impact on median survival and no difference between treatments with respect to duration of remission. Responders did, however, survi- ve longer (44.2 vs 19.4 weeks). CAMP was significantly less toxic overall. The EP regimen has an unacceptable level of ne- ph~toxicity. Excessive toxicity was seen in patients who were initially PS 2 sugge- sting their exclusion from future trials. None of these regimens warrants routine adoption in the non-trial setting.

Do High-Dose Cisplatin Add to the Therapy of Metastatic Non-Small Cell Lung Cancer

(~{NSCLC) ? Hoffman, P.C., Bitran, J.D., Golomb, H.M., Albain, K.S., Skosey, C.A. The University of Chicago Medical Center and Michael Reese Medical Center, Chiaago, Illinois, 60637, U.S.A.

Between January 1981 and December 1983, 103 patients with MNSCLC were randomized to one of 4 treatment programs: high-dose cisplatin (DDP) +vindesine (V) , DDP+etoposi- de (E) , DDP+V+E, or Cytoxan+Adriamycin+Me- thotrexate+Procarbazine (CAMP). Performance status (PS) was < 2 in 87% of patients, and 57% of patients had adenocarcinoma. Among 92 patients who completed two cycles of therapy, the results were:

E-0DP 23 4 13 17 201 VE-DDP 23 13 22 35 291

CAMP 24 4 33 37 234

There was no significant difference in response rate by PS or cell type. The lower response rate for the V-DDP program approach- ed but did not reach statistical signifi- cance (p=.08). Responders had a signifi- cantly longer median survival (306d) com- pared to patients with minor response or stable disease (196d), or progressive dis- ease (93d), p=.001. There was a signifi- cant improvement in median survival for patients with better PS, but no difference in survival according to cell type or treat- ment program. The mean nadir WBC and plate- let counts were lowest for the E-DDP group, but all three DDP-containing programs had lower nadir WBC and platelet counts than the CAMP program. There were 4% drug-rela-

ted deaths. We conclude that while DDP-

containing programs have activity in MNSCLC, and that CP's may be achieved, the advantages may not warrant the increased risk and incon- venience over an outpatient program. However, the higher CR rate in one arm warrants further study of the VE-DDP program. (Supported in part by Eli Lilly Laboratories).

High (120 mg/m 2) Versus Lower (60 mg/m 2 Dose of Cisplatin (CDDP) in Combination With Etopo- side In The Trea~nent of Non Small Cell Carci- noma (NSCLC). Klastersky, J., Sculier, J.P., Ravez, P., Libert, P., Michel, J., Vandermoten, G., Roc- mans, P., Mairesse, M., Thiriaux, J., Dalesio, O., Mommen, P. and the EORTC Lung Cancer Work- ing Party, Institut J. Bordet, Bruxelles, Bel- gium.

High dose CDDP given with vindesine has been reported to be associated in NSCLC with impro- ved survival of responders as compared to a lower dose of CDDP. In order to verify this ob- servation, we randomized 195 evaluable patients between CDDP 120 mg/m @i and CDDP 60 mg/m~dl both with VPI6 120 mg/m d 3,5,7. Courses were repeated every 3 to 4 weeks. Patients characte- ristics were as follows:

High 4oee CDDP Lover dose CDDP Huaber of cases 87 108 Sex H/F 80/7 98/10 Hem ase 61 (34-75) 61 (38-75) P.S. (Karnofeky) 77 (60-100) 77 (60-100) Squaaoua ee11/sdeno- 60/22 66/35 carcinoma i l l tced/dtJeeminsted 38/49 40/60

Result| were as follows : Objective responses 26 (30%) 19 (17.5X) p-.032 Hedlan survival (months)

- overal l 6 7 p'O.53 - l lmlted disease 7 9 p-O.30 - d l s s e u l n a ~ e d d i s e a s e 6 6 p ' 0 . 9 6 - reepondets 13 12 p-0.6§

The high dose CDDP regimen was more myelo- toxic than the other one. Common side effects were nausea, vomiting, diarrhea, alopecia, thrombocytopenia, and leucopenia.

High dose CDDP regimen might increase the response rate in NSCLC but not the survival.

Vindesine/Cisplatin Chemotherapy In Patients With Advanced Non-Small Cell Carcinoma of the Lung. Niederle, N., Alberti, W., Sch~tte, J., Schmidt, C.G., West German Tumor Center, Essen, F.R.G.

Fifty male patients (pts) with inoperable non-small cell lung cancer were given combina- tion chemotherapy + radiotherapy. Cytostatic treatment (q ~ wee~s x 4) consisted of cispla- tin (i00 mg/m ~ as 62hour-infusion) and vinde- sine (either 5 mg/m iv ~olus injection of day i: 15 pts; or 3 mg/m iv bol~s injection on days 1+4: 14 pts; or 1,5 mg/m iv bolus in- jection on day 1 followed by 1,5 mg/m~ as 24 hour-infusion during three consecutive days: 21 pts). 21 pts were additionally irradiated towards primary disease sites with doses up to 60 Gy.

Pt characteristics were: median performance