110

According to these first results we are now carring out a study with D-V regimen as first line treatment in SCLS pts.

A Phase II Study of 0ral VP-16 in Small Cell Lung Cancer (SCLC) in Japan. Matsui, Y., Kado, M., Ohshima, S. Chest Disease Reserach Institute, University of Kyoto, Japan.

The lung cancer group of Nagoya, Kyoto, Ohsaka, Nagasaki, Kumamoto and Okinawa, Japan, initiated a multicenter trial with the objective of examining the anti-tumor effect of VP-16 from October in 1982 to June in 1984.

Evaluable 62 patients with SCLC received treatment with VP-16 in a dose of 200 mg/ body/day, given orally for 5 days. The par- tial response (PR) and PR+ minor response (MR) were respectively 19(31%) and 34(54.8%) out of 62 who survived to receive two more cycles.

The dose limiting factor was leukopenia, while thrombocytopenia in 2 cases. Clini- cal toxicities noted was anorexia, nausea, vomiting, stomatitis, diarrhea and alope- cia and were well tolerated in all cases.

The result indicated that VP-16 has considerable efficacy in SCLC and is use- ful as a drug for combination chemotherapy.

A Cooperative Phase I[ Study of NKI71 (Etoposide) in Small Cell Lung Cancer- Comparison of Results Between the Intra- venous Administration and The 0ral Admini- stration. Arai, R., Kodema, N., Tsuruta, M., Furuse, K., Nishiwaki, Y., Nemoto, E., Komatsu, H., Fukunaga, H. Reporting for National Chest Hospital Lung Cancer Cooperative Study Group, Natl. Kinki-Chuo Hospital for Chest Disease, Sakai, Japan.

A phase II study of etoposide was car- ried out in 13 institutions of National Chest Hospital Lung Cancer Cooperative Study Group in Japan. Twenty six patients (pts) were treated with the intravenous (i.v.) administration of etoposide, 80 mg/m2/ day for 5 consecutive days, and 25 pts wish the oral administration of that, 130 mg/m-/ day for 5 consecutive days.

In the i.v. study, 22 pts were evaluable, of which 8 pts (36%) showed a partial re- sponse (PR). In the oral study, 25 pts were evaluable, of which 7 pts (28%) show- ed a PR. Each study gave a similar response rate. As to previously untreated pts, 6 of 14 pts (43%) responded to the i.v. admini- stration, and 7 of 18 pts (39%) responded to the oral administration, respectively.

The major do~e-limiting factor, leuko- penia (<3000/mm) were observed in 59% pts of the i.v. administration, and in 32% of the oral administration. Other side effects were anemia, thrombocytopenia, a-

norexia, nausea, and alopecia.

It has been concluded that etoposide is an active drug in small cell lung cancer, and the oral administration is better for clinical use than the intravenous administration.

Combination Chemotherapy For Small Cell Carci- noma ~f the Lung: ACN~+VCR+PCZ+ADM+VC~+CPA. Bando ~ H., Yamashit~ , T., Kinosh~ta , S, Ogushi4, F., Tsubura ,4E., Morioka , S., Morita , J., Matsunaga , Y. i. Pulmonary Branch, Tokushima Prefectural Miyoshi Hospital. 2. Third Dept. of Int. Med., Tokushima University, Tokyshima, 3. Pulmonary Branch, Kochi Municipal Hospital, Kochi. 4. Pulmonary Branch, Taka- matsu Red Cross Hospital, Kagawa, Japan.

Comparative study of alternating non-cross resistant chemotherapy, A.V.N.-D.V.C. (ACNU+ VCR+PCZ+ADM+VCR+CPA) was carried out against small cell lung cancer. A.V.N. (A.V.F.) the- rapy and D.V.C. therapy were used as histori- cal control, respectively. A.V.N. (A.V.F.) therapy was composed of ACNU (2.5 mg/kg, day i), VCR (0.02 mg/kg, once every week) and PCZ (i mg/kg, daily) or Tegafur (15 mg/kg, daily), and duration of one course was 6-8 weeks. D.V.C. therapy was composed of ADM (2 mg/kg, day i), VCR (0.02 mg/kg, days 1 and 5) and CPA (2 mg/ kg, days 1 to 5), and repeated every 4 weeks. A.V.N.-D.V.C. therapy was done by a timely alternation of 1 course of A.V.N. and 2 courses of D.V.C. Results were summarized in the table.

A.V.N. D.V.C. A.V.N.-D.V.C~" No. of patients 45 19 23 Age 64~8.7 66*8.2 64.9.1 Stage I-III 23 10 14

IV 22 9 9 PS 0-I 20 I 12

2-4 25 12 11 CR (~} 10(22) I(5) 6(26) PR (~) 18(40) 4(21) 13(57) Response Rate 62 26 83 MST (months} 8.5 5.0 14.0

Clinical Efficacy of The Four-Drugs Combina- tion Ceve in Small Cell Lung Carcinoma (SCLC). Berett~, G., Labianca~ R., Tedeschi~ M., Soresi , E., Borghini-, U., Scoccia-, S., Luporini, G. Medical Oncology Dept., S. Carlo Borromeo Hosp., and i. Pneumology Dept., Nigu- arda Hospital, Milan, Italy.

In patients (pt) with SCLC the routine used 3-drugs combinations (CAV/CMC'/ACE) produce 60-80% objective response, including 20-30% complete tumor regressions more frequently obtained in limited disease (LD). A possible way to achieve higher CR rate consists in uti- lizing more active drugs at the maximum tole- rable doses. From 1983 we started a phase II study with: C i000 mg/mq i.v. day 1

E' 60 mg/mq i.v. day 1 V 1.4 mg/mq i.v. day 1 E 200 mg/mq os days 3,5,7

every 4 weeks, for a total of 6-8 courses; ra- diotherapy was given further to thoracic field after 3rd course in LD pt showing only PR, and to the whole brain in all CR pt. Therapeutic

response and toxicity were defined with WHO

Ill

criteria (Cancer 47: 207). In 49 evaluable pt (33 LD & 16 ED) out of 54 entered, we registered: 13 CR (26.5%) and 34 CR+PR (69.3%), with a median duration of 12+ months (CR), and 5.5 (PR), very similar in LD and ED, and median survival of 12+ months (CR), i0+ (PR), 7.5 (NC), and 5 (PD). The tox- icity appears relevant only at the haema- tological level, with 9 pt of grade 4 leuko- penia, complicated by broncopneumonia in 7 cases (all responded to antibiotic and supportive care). No treatment-related deaths have been observed. No substantial differences are evident examining separate- ly the contributions of the 2 cooperative centers.

Out experience confirms the possibility to obtain high PR and CR rates in SCLC, but no data at present suggest that CEVE has a higher antitumor activity in compa- rison to the classic 3-drugs regimens. A more prolonged observation is needed to fully define the impact of this new poll- chemotherapy in the late outcome of SCLC pt. Abbreviations: A=adriamycin, C=cyclophos- phamide, C' =CCNU, E=etoposide, E' =epiru- bicin, M--methotrexate, V=vincristine.

Small Cell Lung Cancer (SCLC): RanJomized Study With Two Chemotherapy (CT) Regimens in Limited (LD) and Extensive (ED) Disease. A Nhlticenter Study. Nikkanen, V., Jakobsson, M., J~rvinen, M., Nordman, E., Ojala, A., l~.aloheimo, S. Finland.

Two chemotherapy regimens, VAC-VP-16 and VAC were compared in LD SCLC and VAC in ED SCLC. The agents were administered as fol- lows: vincristine (V) i mg/m (max. 2 2 mg) IV on day i, adriamycin (A) 50 mg/m i.~. on day i, cyclophosphamide (C) 750 mg/m 2 i.v. on day i, etoposide (VP-16) 80 mg/m i.v. on day 2,3 and 4, regimen VAC is same without VP-16. In regimen VEC V and C are administered as in VAC E=4-epi-adriamycin 50 mg/m i.v. on day i. All chemotherapy regimens were given q. 3 weeks x 9. In LD radiotherapy (RT), too, was given to in- volved areas to total dose of 48 Gy/6 weeks between 2nd and 3rd course of CT.

Patients were evaluated after two courses of CT and RT in LD and after two courses of CT in ED.

Limited Ex~ensive VAC-VP- 16 VAC VAC VEC

Evatuable cases 9 19 8 12 Complete remlsJion 4 4 I 0 Partial remission 3 12 3 3 CS+PR 7(78Z) 16(84Z) 4(50Z) 3(25X)

The 1-year survival rate of the LD pa- tients was 76% in the VAC-VP-16 group (13 pts) and 61% in the VAC group (21 pts). In the ED study the six month survival rate was 86% in the VAC group (9 pts) and in

the VEC group 57% (14 pts). The acute side-

effects were moderate.

Cyclophosphamide-Adriamycin-Etoposide (CAE) in The Treatment of Small C~ll Lung Cance~ (SCLC). Ardizzon~-, A., Canobbi~-, L., Repetto- L., Pronzat~-, P., Fel~etti-, R., Fara~elli 3, B., Cotell~-, A., Daga , ~.G., Serrano-, ~., Ben- venuto-, F., De Palma , M., Simonassi-, C. i. Istituto Nazionale Ricerca Cancro. 2. Ospe- dale S. Martino. 3. Ospedale Civile S.P. D'Are- na, Genova, Italy.

Chemotherapy (CT) remains the main treatment of any stage SCLC; neither chest or prophylac- tic brain radiotherapy (RT) nor surgery have been reported to clearly improve results of CT. A consecutive series of 24 pts with SCLC entered a pilot study of polyCT; ~reatment s~hedule consisted of C21000 mg/m and A 50 mg/ m on day i, E 120 mg/m on day 1,3,5. Before entering the study, each pt underwent a comple- te staging. On this update 21 pts are evaluab- le for response. The characteristics of entered pts are: median age 60(44-77) median PS 1 (0-3); 12 had limited disease (LD) and 12 extended disease (ED) according to VALCSG. No pt had received prior treatment. WHO criteria were used for judging response and toxicity of tre- atment. Definition of CR for LD required nega- tive computed chest tomography and bronchoscopy 5 achieved CR (23.8%), ii PR (52.3%), 4 SD (19%), 1 PD (4.7%) out of the 21 evaluable pts. Pts with LD entered CR-PR more frequently than pts with ED (91% vs. 33%). Nor PS neither age influenced the chance of entering CR-PR. Median survival of all pts was 28+wks. Pts with LD had a median survival of 30 weeks and pts with ED had io weeks. Main toxicity consisted of nau- sea vomiting and alopecia in almost all pts, leukopenia grade II in 1 and III in i, piastri- nopenia grade IV in 1 pt. PolyCT with C-A-E- as only treatment of SCLC seems an effective treatment even if CR rate rigorously evaluated is disappointing.

Cisplatin and Etoposide (PE) Vs Cytoxan and Etoposide (CE) in The Chemotherapy (CT) Of Advanced Non Small Cell Lung Cancer (NSCLC). Pallotta, G., De Marinis, F., Maccone, C. Pneu- mological Institute "Forlanini", 3rd Division 00149 Rome, Italy.

A total of 65 patients (pts) with advanced NSCLC were treated with cisplati 9 (60 mg/m i. v. d. i) and etoposide 2120 mg/m- i.v.d. 1,2, 3) or cytoxan ~800 mg/m i.v.d. I) and etopo- side (i00 mg/m- i.v.d. 1,2,3). Cycles were repeated every 4 weeks (wks). There were 30 pts evaluable in PE group and 28 pts in CE group. No differences were between the groups with respect to prognostic factors and histo- logic cell type.

After a median of 3 courses given, PE group gave 1 CR, 2 PR and 5 MR for an overall response rate of 26.5% and a median of survival (MS) of 28 wks (144+, 156+) compared to CE

group with 1 PR for a response rate of 3.8%