II study of combination chemotherapy of CDDP and CBDCA in patients with non small cell lung cancer

NEOADJUVANT CHEMOTHERAPY IN NON-SMALL CELL LUNG CANCER: LONG TERM FOLLOW-UP IN A 73 PATIENT TRIAL WITH IIIA STAGING AND NODE APPARENT MEDIASTINAL CLINICALLY INVOLVEMENT. RJ Gralla, MG Kris, N Martini, and KMW Pisters. Memorial Sloan-Kettering Cancer Center, New York, NY, and the Ochsner Clinic, New Orleans, LA USA. 73 patients (pts) with stage IIIA NSCLC were entered into this study. Initial results were presented at this meeting in 1988; med followup now 61mos. Chemotherapy (chemo): 23 cycles of MVP (mitomycin + vinca + cisplatin 120 mg/mZ) then resection in pts with response to chemo. Characteristics: med KPS=80; 56% adenoca, 29% epid and 15% large cell. Chemo resp CR lo%, PR 68%. Of the 58 pts who had surgery, 44 were completely with resected=60% of all pts/or 70% thoracotomy; there were 2 treatment related deaths. Pathologic complete resp in 9 pts. Survivals: all pts/completely resected pts: med surv 19/27 mos; 1 yr 73%/84%; 3 yrs 28%/47%, 4 yrs 19%/ 28%, 5 yrs 16%/24%. Results significantly exceed our historical group treated with surgery + RT. 5 year results indicate: 1) MVP is safe with high response rates in stage IIIA; 2) high complete resection rates occur after response to MVP; 3) response, complete resection, and survival rates support careful randomized future trials.

501 PHASE I/II STUDY OF COMBINATION CHEMOTHERAPYOF CDDP AND CBDCA IN PATIENTS WITH NON SMALL CELL LUNG CANCER AkihikoGemma, AkinobuYoshimura,Kun ihiko Kobayashi, Masahiko Yasuyuki Taniguchi, Kouzou Yoshimori, Niitani Shibuya, :_yis($nobu hi: pon medical Pnani r0,nr.r ;E R Ryo 113 Japan. s expected to increase the ulatinum dose and antitumor activity with acceptable toxicity because of t heil, different toxicity pattern. To evaluate the co mbination effect of CDDP and CBDCA, Human Tumor :,C!“!ogenic Assay (HTCA) was perforced using PC-= aIIIl I C-14, human lun adenocarcinoma cell lines, and the co mbination effec ? was evaluated by medial n+fect,ana!ysis. Results showed it was above adalrlve at mole ratios of about 1-4 (CBDCA/CDDP). We had tried a pha se I/II study of the combination chemotherapy of CDDP and CBDCA (CDDP/ CBDCA) in non small cell lun cancer. Seven teen patients were received CDDP/ ? BDCA in dose finding study (A:CDDP 80mg/sqm + CBDCA 300mnl sqm day1 8 cases, B:CDDP IOmg/sqm + CBDCP L 350m&sqm day1 6 “,;;;;j C:CDDP lOOmg/sqm + CBDLn ” JVV~I~~ ‘““--lsqm day1 3 Patients characteristics wer e 11 males and 6 females media;,;;: $c_xe?rs, PS 0; 1 12 cases and PS 2-3 5 &ases IIIH 4 cases, IV 7 cases and recurrence aft;r reset’ tion 6 cases, 11 adenocarcinomas, 5 squt 3mous cell carcinomas and one carcinoma. Mali”; toxjcjty was ,.+.“rl,. 0-y toxicity f 111s,.Q+.-.n IPLSJ ,,z VI g,auc were ’ iiii:“iii”“iik (B) and 3/3 (C) en patierits were receivea CDDP 80m /sqm + CBDCA !;$I$ sqm therap in and 4 fema r es. S~!~~~~~g”l~~~~6fi/i~~~s~~~~~~~~~~~~~~ ases and PS 2-3 cases, IV 6 cases and recur rence after r§ion 4 cases. There were 12 adenocarcinoma and 7 squamous cell carcinoma. Overall response rate was 8/19 (42.1%). The response rate of no prior chemotherapy cases was 7/15 (46.7%). This results sug ested that this combination of the agents has signi f. icant activity against NSCLC.

R. souh;nri, J. Hartley, R. Allen, R. Rudd, P. &rper and S. Spiro. Depar&nt of (kroloey, University College and fiddlesex school of &dicine, Londcsl WlP m, Lndcn Chest I&spital, Bran~ton Hospital and Guy’s Hospital. 49 ptients (pts) with advanced, histol~ically confirmed, untreated m me entered into a phase II study of 10-EDAM. ‘Ihe IIEZI ale = 63y (range 39-74), kw3 status = 0:24 pts, 1:18 pts, 2:7 pts. ‘Ihere were 352n&s. 10-m w siven es a weekly b&s injection of X&/m . r&e I-Eductions weremde for trade 3 or 4 tnzcositis or myel~ppression, and dm delay for trade 1 or 2. 12 cycles we given if there lzes no excess toxicity or disease pr~ression;. m was assessed at 4, 8and12&(~criteria). After 12 w&~ Btients were e&ible to receive a further 6 cycles every 2 4~. Of the 45 patients el&ible for rm assesslPnteputialres_ was obtained in 6 (13.3, 95% confidence interval 6-26%) and a minor rezpcmse in a further 9 (Zj%, ll-34%)). htion of the~ialres~-10weeks(~e4--40he&s). Toxicity lr~s dy mositis (grade 3 or over in 21%). ?he drug was eliminated rapidly (t+B = 40 minutes). &area&r the plasma concentration curve (AUC)was accurately predicted by a si&e measurement at 1 hour. Toxicity or dose delay occurred in patients ti 1 hour plazim concentration exceeded *l on the first cycle. lhis study confins ti-& 10-m is active in NSCLC. bitis is the ti toxicity and is rrure likely in ptients &ase 1 hour plasra level is above 2~1.

502 P-GLYCOPROTEIN EXPRESSION IN TREATED AND UNTREATEDHUMANLUNG CANCER Akihiko Gemma, Shoji Hisakatsu, Yasuyuki Taniguchi, Satsuki Wasai, Hisanobu Niitani Department of Respiratory disease, Nippon medical School, l-l-5, Sendagi, Bunkyo-ku, Tokyo 113 Japan. There are little report that showed the expression of P-Glycoprotein in treated human lung cancer because of the difficulty of obteining sufficient materials. The expression of P-Glycoprotein in treated and untreated human lung cancer was investigated by means of immunohistochemistry, using a monoclonal antibody (MRK16) and a polycional antibody (MDR ab-1). The frozen sections of tissues from autopsy were stained by ABC method. Twenty-nine patients was treated with chemotherapy and the other 11 patients received no chemotherapy, Twelve of 22 tumors shown clinically resistance to chemotherapy had reactivity against MRK16, while only two of 12 tumors untreated or being seusitive to final chemotherapy (p