Ifosfamide, cisplatin and etoposide in advanced non small cell lung cancer

Ifosfamide, cisplatin and etoposide in advanced non small cell lung cancer

129 493 494 AMBULATORY CONTINUOUS INFUSION OF FLUOROURACIL (WITH/WITHOUT CISPLATIN), BY MEANS OF PORTABLE PUMPS IN NON-SMALL-CELL LUNG CARCINOMA (NS...

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129 493

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AMBULATORY CONTINUOUS INFUSION OF FLUOROURACIL (WITH/WITHOUT CISPLATIN), BY MEANS OF PORTABLE PUMPS IN NON-SMALL-CELL LUNG CARCINOMA (NSCLC). AV Bedini. L Tavecchio, M Valente, G Ravasi. lstituto Nazionale Tumori, Via G. Venezian 1, 20133 Milano. Italy. We tested feasibility and effectiveness of Fluorouracil-based chemotherapy (CT) given in continuous venous infusion (CVI) by a low-toxicity means of a portable pump, with the aim of planning regimen to be delivered on an outpatient basis. Pts with NSCLC staged lllb non-irradiable with curative intent for supraclavicular spread or malignant pleural effusion, or IV were entered on 2 consecutive pilot-phase II studies from Nov. 1989. Twenty-eight pts (8 staged as lllb and 20 as IV) entered the 1 st study. Treatment schedule consisted of CVI, 24 hours a day, of FU, given at a daily dose of 300 mg/m2 on 20 days (3-7, 1 O-14, 1721, 24-28), alternated with Cisplatin (CDDP), delivered at a daily dose of 8 mg/mZ on 8 days (l-2, 8-9, 15-l 6, 22-23), q. 35 days. Two cases of grade 3 toxicity were registered. We obtained 3.5% complete response (CR), 32.1% partial responses (PR), 60.7% stable diseases (SD) and 3.5% progressions (Pro). Median time to progression (MTP) was 22 weeks, and median survival (MS) was 48 weeks. One-year survival was 40%. In a subsequent study FU alone was given at the same daily dose, dose-intensity, and by the same delivery mode, on days l-10 and 15-24, q. 35 days. Fourteen pts were enrolled before stopping accrual. Six had stage lllb disease, the remaining 8 with stage IV. No case of grade 3-4 toxicity was assessed. Seven% PR, 35.7% Pro, 57.1% SD were observed. MTP was 7 weeks. Nine pts were submitted to the former regimen including CDDP at progression, obtaining 2 PR, 4 SD, 3 Pro. MS was 35 weeks. Oneyear survival was 21%. FU alone in CVI is ineffective in NSCLC, but the addition of CDDP to FU seems to have activity with a response rate of 35.6%, and negligible toxicity. Treatment can be given on a full outpatient basis, and about one-half of the patients can be trained to self-administration.

I?OSF/MIDE, CIS?LP."IN!idDETOPGSIDE :A LDWNCED

495

C Camps, Unidad de Valencia.

NGM SM!!>:i

A.Berrocal,J.M.Vicent,M.Godes. Oncologia

MCdica.

%spital

seneral

Univers,:ario

Espafia.

Cbjctiw: 'lia~the efectivity of ifosfamide,cisplatin and etoposide (1CE)in advanced non-small cell lung cancer (ANSCLC) and evaluate its toxicity. and methods: 33 patients with histologically Patients proven ANSCLC (inoperable o metastatic disease) were ente red to study.Median age was 59(30_70),male/fewale ratio 30 /3.Distribution according to:l)histology was epidermoid 26 adenocarcinoma 6 and anaplastic la~o,ecell 1,and 2) stage IIIA 2,IIIB 20,IV 11. Median Karnofsky was 80%(60-90%). Therapeutic scheme was cisplatin 60 mg/m2, etoposidelO0 mg/m2 and ifosfamide 17OCmg/m2,the firts on day 1 and the others days one tc~three. Courses every 21 days for 3 and if response assessed 2 additional courses and if residual disease was confined to thorax radiationwas added. Results: respose rate of 25%(all partial) was observed (95% CL ll-45%). Almost all responses were observed in patients with IIIB stage(6/7) and only one in s&age IV (p=n$ Median overall survival has been 5.7 months.According to response was 3.5 m. for non-responders and non reached (5 patients still alive with a follow up between 6 and 15 m) for responders (Log Rank Test p less than 0.001). Marrow supression was the dose-limiting toxicity.Leucopenis G4 in 7 patients and thrombocytopenia in 3.The media n nadir granulocyte count was 300(200-18OO)/mm3.Non hemato logic toxicity was modest,alopecia G3 in all patients and nausea/vomiting G3 in 30%. CONCLUSIONS: ICE has a modest activity in ANSCLC with si nificant toxicity.The increase in etposide dose only ad%s toxicity compared to previously reported.

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RRCOWINANT BUYAW ImRLEUKIN 4 (IL-4) SCH 39400 IN NONS&g&I& CRLL L”NQ CA”CRR (NSCLC): RRS”LTS OF A PSASE II INWSTIQATION. H.Hochster, W. Lotte, R Figlin, ME Rybak U. E. Vokes, Chicaoo. Chicaao IL, NY Univ. New York. NY, U.

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Pitt&&gh, Pi&sb&gh PA, U&A, Los Ahgel& CA, Schering Plough Res Inst. Kenilworth NJ IL-4 is a pleiotropic cytokine with antitumor activity in animal models and Phase1 trials. A randomized phase II study of 2 doses of IL-4, (O.ZSus/ks and i.Opg/kg), ad&nistered subcutaneously +.I;W; was conducted in advanced NSCLC. Thirty-two patients(pts) have bee" enrolled on study, received at least 3 doses of IL-4 and have follow-up data. Median age was 60 and 63 years for the groups. Histologies were balanced between groups with 22 adenocarcinomas, 6 eguamous cell and 4 other NSCLC. Stage of diagnosis was 1116 in 3 pts, and IV in 29. Pts had a performance status of O-2. Twenty-five pts received prior combination chemotherapy, predominantly cis-platin based. IL-4 was well tolerated, with no IL-4 associated changes in CBC, liver enzymes, bilirubin, blood glucose or other serum chemistries. The most frequent symptoms in the 0.25pg dose were fatigue(9/15), fever (4/15), rigors(3/15), anorexia There were 2 severe adverse reactions: 1 (4/15). vomiting and 1 dyspnea. In the l.Ol.rg group, a similar toxicity pattern was seen: fatigue (5/17), fever (6/17), anorexia (3/17), naueea (3117). pruritus (3/17). There was 1 severe hypotension and 1 chest pain. One pt withdrew with a perforated ulcer. Twenty-four patients have data available for analysis of response. Antitumor activity was seen with an apparent dose response. The 1.0 I.rggroup had 1 PR >540+days duration and 4 pts with stable disease(SD): >340+, >290+, 174, and 50 days duration. Of these 5 pts, all had stage IV disease and 3 had progressed on prior chemotherapy. In the 0.25pg group, 2 pts had SD of 106 and 97 days. These data suggest that rhuIL-4 has antitumor activity in NSCLC. IL4, alone or in combination with other cytokines and chemotherapy should be further explored in NSCLC.

ANDCARBOPLATININCOMBINATlONINSTAGElVANDlIIBNON SMALL-CELL LUNG CANCER (NSCLC): A PHASEUTRIAL. C.J.Langer.J.

TAXOL

Leighton. R. Comis. C. McAker. C. Bonio. P. O’Dwyer. R. Scber. M. wn Mebno, I. Reda. E. J&old. P. Eogstmm. S. Shore. R.-ALexaoder, R. 0~01s. Fox Chase Cancer Center (FCCC), Phila., PA 19111. Taxal has producedthebestresponserate (21%) iodateof811single ageotsin ECGG trials in NSCLC. witi its activity coofumed 81M.D. Anderson (JNCI 85: 384.388. 388-394.1993); in a randomized ECGG study of c~splatm analogues and combinations. imtial therapy with carboplatin resulted in the best I year survival (JCO 7: 1602-1613. 1989). In 6/93. we initiated a phase lJ tial of taxoVcarb+platio in patients (pts) with stage Iv oI effbsmn(+)atage IIJ NSCLC; mewrabledircase:ECOG P.S.Oor l,ANC~20C0/mm3: platelets 2 JC0.KQ/mm3: aeat. 5 1.5 mg/dk bilimbii 5 2 mgldl; no prior c41ematbempy: and previous XRT reshicted to 5 3096 of mmmw lxaring bow Tax01 was ioitially dosed at 135 mg/m2/24 ix followed by carboplatin with dose based on a targeted AUC of 7.5. Trealmetd was repeated at 3 week inrervals for 6 cycles. GCSF 5 mc@kg6cdays 3-17 was in!mduced during the 2nd and subsequent cycles with fax01 dose secweotially escalated fo 175-215 mg/m2 in patients suslai&g < bade 4 myelosuppress& 36 pt; have been enrolled a1 FCCC and its network affiliates: 17 are currenlly evaluable for foxicify. 16 for respoose. Median age is 61 (range. 46-73); 70% are male: 70% have adcocarciooma sod 88% stage IV disease. Myelasuppressioo has been the prmcipal toxicity wilb grade 314 granulwytopeoia occunina in 70% after the 1st cycle, bul decreariog to 35% after the 2od Cycle with the inhoductiaobf G-CSF, and then c&sistenLly ( 10% af&r the 3rd. 4tb and 5th cvcks wrfh continuahoo of G-CSP. 001~ 14% of cycks have been delayed 1 we& or more. i&utropenic feverhaaoccurred in4 (596) of 77 e&able cycles. &grade 34 toxicities mclude anemia (9%). thrombocytopnia (9%), fatigue (9%) and lwmorrbngic cystitir (1%). Taxol dose has been boosted to 215 mg/m2 m 1207 70%) pts by cycles 3 ~4. At AUC of 7.5. median 1st cycle carboplatin dose is 434 mg/m 1 (range. 314-709 mg/m2). Objective response rate is 56% with 2CR. 7PR. and 1 MR. Conclusion: Tbe fuoUcarboplatm combinatmn 1s aeWe in advnoced NSCLC and. with AUC-based dosing of carbeplatin, can be given at J-week intervals. Gmmdocytopeoia IS dose-limiting 81 a tax01 dose of 135 mg/m2. but can be reduced substantiall with GCSF. allowing sequential dose escalations of tax01 to 175 mg/m2 and 215 mg/m s. 10 2 50% of patmots receiwng 3 or more cycles. Follow-up study will evaluate a infusion of tsxol imtiati at 175 mg/m2 in combination with cartoplatin at AUC of 7.5. Suppried in port Ly czneducorionol granrfrom Br&&Mycrs Squibb