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ETOPOSIDE AND HIGH DOSE CARBOPLATIN IN PREVIOUSLY UNTREATED PATIENTS WITH SMALL
CELL LUNG CANCER (SCLC). D C TaIbot, A L Jones, I E Smith. Lung Unit, Royal Marsden Hospital, Sutton, Surrey, UK
We have previously shown that high response rates iu SCLC cau be achieved with carboplatiu and etoposide at conventional doses. The aims of this study were to iuteosify the dosage of this combination in tit, previously untreated patients (pts) with SCLC and to assess the impact on response duration and survival whilst maintaining acceptable toxicity. Treatment courses were repeated every 28 days with carboplatiu 600 mg/m’ iv day 1 and etoposide 120 mg/m’ iv days l-3 for courses 1 & 2; dose reduction of carboplatio to 400 mg/m’ iv day 1 and etoposide 100 mg/m’ iv day l-3 were made for courses 3 & 4. AU pts received prophylatic antiemetic therapy. Patients achieving CR were offered prophylactic cranial irradiation.
22 patients have been entered into this ongoing study, aII of whom are evaluable for response and toxicity. Patient characteristics were: male 14 (64%). median age 59 years (43-74), limited disease 13 (59%), median WHO performance status 1 (O-2). Response: CR in 4/22 (18%) all of whom had had limited disease (LD), overall response rate 19/22 (86%, 95% confidence interval 72-100%). Median response duration, LD 11 months, extensive disease (ED) 6 months; median duration of swvivaI LD 12 months, ED 8 months. Toxicity (WHO grade 3-4 as % of courses): anaemia 9%, leucopeuia 73%, thrombocytopeuia 86%, infection 22%, emesk 9%. mucositis 5%, diarrhoea 5%, alopecia 59%, nephropathy 5%, neuropathy 0%. Dose reductions: 5% of pts had a 25% dose reduction for their 2nd course owing to leucopeoia.
This study demonstrates that dose iuteusification with carboplatin and etoposide has not sigoiticautly affected the response rate iu SCLC or as yet led to advantage in median response duration or median duration of smvivaI.
ROLE OF LEUCOVORIN (LV) FOR EDATREXATE Q, CYCLOPHOSPHAMIDE (C) AND CISPLATIN (P)
REGIMEN. JS Lee, FV Fossella, HI Libshitz, WK Murphy, A Pang, SM Lippman, BS Glisson, DM Shin, IW Dimery, WK Hong. M.D. Anderson Cancer Center, Houston, TX 77030. E is a new antifole with promising antitumor activity in non- small cell lung cancer (NSCLC). Using a new ECP regimen (E on days 1 & 8, C and P on day 1, repeated every 3 wks with dose modification), we treated chemo-naive pts with stage IIIb or IV non-small cell lung cancer (NSCLC). All pts had adequate major organ functions and Zubrod’s P.S. of 2 or less. The original schedule with respective initial doses of 80-800-80 mg/m* yielded a 47% response rate (7/15 evaluable among 16 pts) but with significant stomatitis and myelosuppression. A subsequent schedule with reduced starting doses (70-700-70 mg/m*) was better tolerated but the response rate dropped to 27% (4/15 evaluable among 16 pts) (Proc ASCO 9:241, 1990). Median survival for all 32 pts was 38 wks. To see if LV could improve the therapeutic index of this regimen by modifying the dose-limiting toxicity of E, we treated an additional 15 .pts using the initial dose schedule (80-800-80 mglm2) plus LV (15’mg p.o. x 4, each 6 hrs apart starting 24 hrs after E). Major response rate was 43% (6114 evaluable pts). This latter group of 15 pts had lesser degrees of stomatitis, received more E, and also survived longer than the 32 pts treated without LV @=0.047), with 8 pts still alive after minimum followup of 48 wlcs. These results suggest that ECP is an active regimen for NSCLC and that LV improves its therapeutic index.
ARANDOMISEDTRIALCOMPARINGALOWTOXICITY REGIMEN (CARBOPLATIN, VINBLASTINE &
METHOTREXATE (CVM) AGAINST ADRIAMYCIN, CYCLOPHOSPHAMIDE & ETOPOSIDE IN SMALL CELL LUNG CANCER (SCLC). A L Jones, I E Smith, Lung Unit, Royal Marsden Hospital, S&ton, Surrey, UK
Long term survival is rare iu SCLC and for most patients (pts) the aim of treatment is palliation of disease related symptoms through objective remission. We have therefore developed a low toxicity regimen CVM: carboplatin 300 mg/m2, viublastiue 6 mg/m’, methotrexate 30 mg/m’ iv q 28 days and compared it with a conventional regimen ACE: Adriamyciu 40 mg/m’, cyclophosphamide 600 mg/m’, etoposide l&l mg/m” (Dl-D3) iv q 21 days in a prospective raudomised trial. AU pts received prophylactic a&emetics with metoclopramide and dexamethasone. 104 pts were raadomised (CVM 54 : ACE 50) with no difference in baseline characteristics or stage. The objective response rate was 67% (95% confidence limits [CL] 54-79%) for CVM and 88% (45% CL &?-97%) for ACE (p = 0.06) with a complete response (CR) rate of 13% for CVM and 12% for ACE. For limited disease (LD) the response rate was 83% (24% CR) for CVM (17 pts) and 93% (27%) for ACE (15 pts) (NS). Despite a difference iu overall response there was no significant difference in median response duration for CVM 6 months (mo) (95% CL 5-8) and ACE 5 mo (95% CL 3-6) or in overall survival CVM 8 mo (95% CL 7-10) and ACE 7 mo (95% CL 4-9). Crossover response to second line chemotherapy was 18% for CVM and 56% for ACE (p ~0.05). Grade 3/4 haematological toxicity by course was as follows: leucopeuia CVM 2O%, ACE 80% (p <0.005); thrombo- cytopenia CVM 2% : ACE 12% (p = 0.01); anaemia CVM 0% : ACE S%(p <O.OS). TherewasareductionininfectionCVM6%:ACE35% (p < 0.001) and alopecia CVM 2% : ACE 68% (p < 0.001) but no difference in emesis/mucositis.
CVM is an activewelltolerated regimen&able for outpatient use in SCLC and has less toxicity than a conventional ACE regimen.
. . b_ ~tialofcytotauclty of v by cyWuW!sinwsm?lLlcel11Imgczlna?r. A randanized phase II study.
Maasilta P, Holsti LR, Pyrhtjnen S, Halme M, Mattson K Departments of Pulmonary Medicine and of Radiotherapy and Oncoloqy, Helsinki University Central Hospital, Helsinki, Finland. Hmo(-IFN has been reported to potentiate the anti- tour action of chewtherapy in non small cell lunq cancer xenoqrafts (Cancer Res 47, 1986). To test this concept in a clinical setting we are conducting a 3 armed randanized phase II study on previously untreat- ed patients with non small cell lunq cancer: Arm I ch= alone, Arm II chemo plus qanma-IFN, Arm III chemo plus qanma and alpha-IFN. The chmerapy consisted of cisplatin (P) 60 T/II-? d 1 and etoposi- de (vp16) 100 q/m2 dl, d3, d5, q 28 d x 6; anma- IFN (rIFN#Q) was given at a dose of 0.2 mg/m 8 S.C. TIW and alpha-IFN (rIFNw) at 6 x 106 IU S.C. TIW. Both IFNs were given from dl over 6 nrxlths. Of 62 patients so far entered in the study the re- sponses of 41 have been evaluated: Arm I 5/14 PR, Arm II 4/15 PR, Arm III 3/12 PR. Median time to pro- gression for respcmders was: arm I 23 weeks, arm II 40 weeks and Arm III 25 weeks. Toxicity was mild in all treatment arms: qrade 3 reversible leukopenia in 13 patients (Arm I 2, Arm II 2 and Arm III 9) and grade 3 reversible Bia in 2 patients (Arm 111). Treatments were given on an outpatient basis and were readily accepted by the patients, including those in the mined treatment arms. We plan to continue this study until we have at least 20 evaluable patients/ arm.