Abstracts/Lung Cancer 10 (1993) 123-150 143

mclude studies of platinuml etoposide plus new agents. Also a study

comparing platinum/etoposide versus supportive care should be

considered. The objectives of this study would be to compare SurviveI. quality of life, and cost-effectiveness ratio. The results of recent phase II studies in stage III NSCLC patients suggest that preoperative

cisplatin/etoposide and concurrent thoracic irradiation should be

consideredforevaluation inaphaseII1 trial instageIIlaNSCLC patients and that this regimen should also be evaluated in stage IIIb patients.

CiipItttinlcarImpIatin lhempy io nott-sztt8II eelI lung cancer Niitani H. Kobayasbi K. Dcpr of Founh Internal Mc&ine, Nippon

Medical School, Sendagi. 1-1-S Bunkyo-ku. Tokyo 113. Oo~~logy (Switzerland) 1992;49:Suppl. 151-6.

Based on in vitro experiments suggesting cytotoxic activity of at least P supra additive effect a phase I cliical shuly of carboplatinlcisplatin sequential combiioo treatntent was carried out in I7 patieats with non-small cell lung cancer (NSCLC). At 300 mg13 carboplatin and 80 mg/m’ cisplatin, the median leukocyte nadir was 2.6 x 10411; half the patients exhibited grade 3 or higher leukopmia. when cisplatin was increased to 100 mg/4 the leukocyte nadir fell to 0.7 x loS/l and grade 3 or4leukopmiaw~univerul. Apbasellpilot studyofcarboplatin 300 mg/3 followed by 80 mg/mZ cisplatin was subsequently initiated in patients with NSCLC. Currently. I 1 patients have entered the study and 8 have bean added from the phase I shtdy. Interim analysis shows that 8 prtieatshs~e~~leost~p~iialresponsetocisplntin/cPrboplati~ for a response rate of 42%. The response rate in previously untreated patientswas47%. Atthistime, 12patientsarealivehut mediansurvival has not yet been reached. No particularly serious adverse effects were observed. Four to five repeat administntions are plumed in responders. Future studies with tbe cisplatin/carboplatin combination in NSCLC are warmated.

Preliminary Jobnmm DH. Hainswmtb JD, De Vore R, Hands KR, Grew FA. Divi.rionofMadcalOncology, Vanderbib UnivSchoolofbfuficinc, lhc Va&ilr Clinic, Nwhtille, TN37232-5566. Oncology (Switzerland) 1992;49:Suppl 157-62.

Forty-hvo p&ients with unresoctable non-small cell lung cancer (NSCLC)weretreated witbcarboplatin(300,3500r400mg/~)and21 days of oral etoposide (SO mglm’lday). Tbitty-three patients were evaluble for rapowe (too early to assess the remaining patients) and 9 patients (27 96) achieved a p&al remission. Median survival was 29 weeks (ratwe, 4+ to 71+ weeks). Tbe primary toxicity was myelw

2i ;lld 29. In cycle i , leukocyte nadir ~0s 2.8 x 10+/l nod the platelet nadir was 142 x IOX Nonbematologic toxicities were modest and iacluded alopecia in aII pstlmts, mild nusen, mild to moderate diarrhea. and an occasional increase in serum creatinine. Carboolatin

againstum&ctableNSCLC. . -

PIatinua/oraI cloposido therapy in non-smaII all lung cancer Fums.z K. Lkpanmenr of huemu Medicim, Nat Kinki Central Hasp/ Che.wDi.s., 1160N&awnw&o. Sakai, Osaka. Gnwlogy (Switzerkmd) 1992;49:Suppl. 1:63-70.

Encouraging response rates have been observed with long-tentt daily administration of oral etopmide to treat lung cancer. Reuvlos why EP (etoposide/ cisplatin) has been used to treat non-small cell lung cancer (NSCLC). despite the f&ct that ctqnside has demmstmted only a modestdsgneof~tivity~thisdiasl8c.uaprslinicrlsuggcstions ofcispIatin/e&p&leF+wrgimwndsucca&Irraultsforthe~m it, t,‘&bX Sd WR IUnn UllccT (SCLC). We Wd&. hR_tcrm

this phase I study of 22 patients (I 8 evaluable), we observed partial responses (PRs) in 4 patients, 1 each with uterinecancer and SCLC, and 2 with squamous cell lung cancers. We then designed a phase II pilot study in patients with advanced NSCLC. The recommended treatment schedule is 80 mg/3 i.v. cisplatin on day 1 plus 40 mg/m’/day oral etoposide for 21 consecutive days. Of the 13 evaluable patients, PRs were observed in 4 (30.8%). in 2 patients with adenocarcinoma and 2 with squamous cell carcinoma. None of the side effects were severe or life threatening. Nearly all of the projected doses were grven, with delays of 7-10 days. In this pilot phase 11 study, the response rate of advanced NSCLC ~88 above 30 96. Fuhlre studies should combine long- term administntiw of oral aoposide with radiation therapy or surgery to treat stage III NSCLC.

Expression of several resistance mechanisms in untreated human kidney and lung carcinomas Volm M, Mattem I, Efferth T. Pommermke EW. German Cancer Research Center, Im Neuenheimer Feld 288. D-6900 Heidelberg 1.

Anticancer Res 1992;12:1063-7. Thirty human renal cell carcinomas and 94 non-small cell lung

carcinomas of previously untreated patients were analyzed for the presence of P-glycopmtein. glutatbione S-tmnsferase-Pi and topoiso- meraseU by meansofimmuoohistochemistry. lnthermalcelI~arcir~~mas investigated, two resistance markers were seen in 53% and three resistance markers in 36 % of the cases. In only three tumors was one resistancenxxhanismobserved. Inthe94aon-smallcelllungcarcinomas 34%hadhvoand20%th~resistancemechanisms,wbereas24%ofthe hmmrs revealed only one resistance mechanism. For determining the resistance of the tumors against drugs M in vitm short-term test was used. only 12% of the sensitive lung ttmmrs had more than one resistance mechanism, whereas 70% of the resistant hmtors did. Thus a significant relationship exists behvem the resistance measwed in vitro and the overexpression of P-glycoprotein or glutathione S-transferwe- Pi and the down-regulation of topoisomerase II.

CPT-11: A new derivative of camptothecin for the twabnent of retrpetory or relapsed SmaIl-cell lung cancw Mssuda N, Fukuoka M, Kustmoki Y, Matsti K, Takilitji N, Kudoh S et al. Deparhnenr of huema Medicine, Osaka Prcfcnural Habikino

Hospital, 3-7-l Habikino, Habikino Osaka 583. J CIin Oocol 1992;10:1225-9.

Purpose: To evaluate the activity of CPT-11, which is P new derivative of camptotbecin, against refractory or relapsed small~ell lung cancer (SCLC). Ptztienu and bferhodr: Sixteen patients with refractory or relapsed SCLC were entered onto a prospective. nonrmdomi?.ed, single-institution phase II trial. All 16 patients had been pretreated heavily with some form of cisplatin-based combination chemotherapy. Fivepatieats had received previous chemotbempy with cispIatin, vinctistine,doxorubicin, nndetoposide(CODE)asattindwtion therapy. Six @imts bad been treated with concurrent cisplatin and etoposide plus ch@ x-ray. The median time off chemotherapy was 7.3 months (range, 1.9 to 15.1 months). Patients were treated with P CPT- 11 starting dose of 100 mglm body surface given as a 90-minute intrave-nous (IV) infusion every week with subsequent doses based on toxicity. Fit&en patients were assessable for toxicity, response, and survival. Rcsulrs: Seven patients (47%; 95 % confidence limits for an ovenll response rate, 21.4% to 71.9%) responded to CI’T-II with a median duration of reqnmse of 58 days. The major toxicities were

. . . ” ,, ~~ ~~~..~, ~~_r___._.,

toxicity. Conclusion: Cm-1 I is M a&e agent against refractory or relapsed SCLC and deserves to he studied more closely as both D single

agent and in combiition with other drugs to treat patients with SCLC.

Goi course &i&d if cisplatin on day 1 and et&side from day 1 through day 21. The course was rqakd, beginning at day 29. We concltukd that the maximum tolerated dose in this schedule was 50 mg/ m’/&y onl etoposide for 21 days plus 80 mglm’ intravem~us (i.v.) cisplatin on day 1. lhe major dosaliting toxic off&t was myelo- supprcssioll,pndmucositisw~~msignifiuotinsoms~tients.During

Relation&p of inherent resistance to doxorubin, proliferative activity and apnssion of P-glympmtein 170, and glutalbione S- tmmferase-a in human lung ttmmm Volm M, Mattetn J. Samsel B. German Cam-w Rewarcb Cenrer, Department of Eaper+mcnral Padwlogy. Im Neunluimer F&i 280. D- 6900 Heidelberg. Cancer 1992:70:764-9.