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Since 1987, we have evaluated carboplatin alone or in combination with etoposide. in two separate phase II trials of patients with non-small cell lung cancer (NSCLC) who had not received prior chemotherapy. Single-agent carboplatin produced a 20% response rate in 51 patients treated with 390 mg/m2 intravenously every 4 weeks. A S-day schedule of etoposide 140 mg/m* on days 2,3, and 4, and carboplatin 150 mg/m* on days 1 and 5 also resulted in a 26.7% response rate in 46 patients. Myelosuppressive toxicity associated with carboplatin/etoposide was substantially greater than mat seen with carboplatin alone. Carboplatin asasingleagentisactiveinpreviouslyuntrea~patientswithadvanced NSCLC. The two-drug combination of carboplatin and etoposide also shows activity in NSCLC similar to other combination chemomerapeu- tic regimens based on comparable prognostic factors in untreated patients. Further evaluation of carboplatin as part of combination chemotherapy in NSCLC is warranted.

A randomized trial of two platinum combinations in patients with advanced non-small cell lung cancer: a preliminary report Klastersky J. Sculier J.P. Dabouis G et al. Service de Medecine et Laboratoire d’lnvestigation. Clinique H.J. Tagnon, Institut Jules Bor- det, Centre ties Tumeurs de r Universite Libre de BrueUes, 1 Rue Heger-Border, 1000 Brussels. Semin Oncol 1990;17:Suppl2:2O4.

A randomized study with cisplatin (120 mg/mz) or carboplatin (325 mg/m’) plus etoposide (100 mg/m2, days 1 to 3) in 162 evaluable patients with advanced non-small cell lung cancer (NSCLC) compared responseand survivalaftertrcatment. No statistically significantdiffer- ence in survival rates was detected; median survival was 25 weeks for patients receiving cisplatin and 24 weeks for those receiving car- boplatin. The objective response rate was 25% for cisplatin plus etoposide and 20% for carboplatin plus etoposide. Granulocytopenia, diarrhea, and nephrotoxicity were significantly more frequent with cisplatin plus etoposide than with carboplatin plus etoposide. Severe nausea and/or vomiting occurred during 59 of 77 courses (77%) with cisplatin and 48 of 75 (64%) with carboplatin (I’ = .13). Unlike cisplatin plus etoposide, carboplatin plus etoposide was administered on an outpatient basis. At the dose used in the present study, carboplatin plus etoposide was as effective as but less toxic than cisplatin plus etoposide for NSCLC and could be given more easily.

Phase II study of lonidamine in non-small cell lung cancer: Final report Kokmn 0, Maca S, De Gregorio M, Ciottoli GB. Ludwig Boltzmann Institut tiu Klinische Onkologie, Vienm. Br J Cancer 1990;61:316-8.

Ionidamine f&ND) is a new anti-cancer drug which interferes with the energy-yielding processes of turnout cells without affecting DNA replication. A total of 69 previously untreated patients with non-small cell lung cancer (NSCLC) entered this study. LND was given orally as a single agent at doses ranging from 450 to 900 mg day-’ until turnour progression (2 to +1,042 days). Partial responses (PR) occurred in 7/69 patients (10.1%); 4/25, l/27 and 2/9 for epidermoid, adenocarcinoma and large cell cancer respectively. PR by stage was 4/10,1/3,1/20 and l/28 for stages I, II, III and IV, respectively. The median duration of response was 303 days (+ 6 1 to +338 days). The median survival for the whole group was 261 days. Toxicity was assessed in all patients. NO myelosuppressionoccurred. Themainside-effects weremyalgia(68%), loss of appetite (23%). asthenia (20%) and testicular pain (13%). Doses above 450 mg day-’ produced more severe side-effects without any improvement in therapeutic activity.

Flow cytometric analysis of the kinetic effects of cisplatin on lung cancer cells Fujikane T, Shimizu T, Tsuji T, Ishida S, Ohs&i Y, Onodera S. The First Department of Internal Medicine, Asahikawa Medical College. Asahikawo 078. Cytometry 1989;10:788-95.

The effects of cisplatin on the cell cycle and DNA synthesis of human lung adenocarcinoma cell line PC-9 were examined by flow cytometry.

The cellular DNA content and the bromodeoxyuridine (BrdlJrd) incor- poration rate were measured simuhaneously using a monoclonal anti- BrdUrd antibody. Following exposure to cisplatin (l.Opg/ml) for 1 and 24 hr. the bivariatwe DNA/BrdUrd distributions revealed a delayed S- phase transit and an accumulation of cells in the G,M phase. The BrdUrd-linked green fluorescence intensity continued to decrease with the lapse of time. However, early- and mid-S-phase cells soon recov- eredDNAsynthesisactivity,andtheformershowed higheractivitythan the control cells. These findings suggested the vigorous DNA synthesis of cells in early S phase. However, for quantitative analysis of chemoth- erapeutic effects, some problems remained to be resolved regarding the condition for DNA denaturation and its alteration by the agents.

Phase II trial of CDDP and 5.FU in epidermoid and undifferen- tiated lung cancers Riviere A, Abouz D, Ayela P et al. Centre Francois-Baclesse. Route de Lion-sur-Mer, 24021 &en Cedex. Bull Cancer 1989;76:1095-1102.

The aim of this study was to test cisplatinum and 5-FU chemother- apy. Thirty-five patients with epidermoid or undifferentiated lung carcinoma were entered in a multicentric phase II trial, in an attempt to further define the activity and toxicity of this association. None of them had been previously treated by chemotherapy. The dosage schedule was cisplatinum 100 mg/m’D 1 and 5-FU 1 g/m’ Dl to D5 every 3 weeks for 3 courses before evaluation. There were CR2, PR: 10, for a total response rate of 35%. Median survival was 7 months. Tolerance was acceptable. We conclude that this association can be safely admini- stered, but that the results are not superior to others previously reported. Further studiesare required todefine theactivity ofacisplatinum. 5-N and radiotherapy association.

A novel pharmamdynamically based approach to dose optimiza- tion of carboplatin when used in combination with etoposide Belani CP, Egorin MI, Ahrams JS et al. Division ofMedical Oncology. University of Maryland Cancer Center, 22 South Greene Street. Balti- more, MD 21201. J Clin Oncol 1989;7:18%-1902.

Thrombocytopenia, the dose-limiting toxicity of carboplatin, is manageable and predictable with the dosing equation: Dose (mg/m’) = (0.091) (creatinine clearance)/(body surface area) (desired percentage change in platelet count) + 86. We used this equation to dose patients receiving carboplatin (day 1) and etoposide (80 mg/mzdays 1 to 3). An initial cohort of 14 patients with non-small-cell lung cancer (NSCLC) were treated with 75% of the calculated dose of carboplatin (29 evaluable courses) as a precaution against added myelosuppression from combination chemotherapy. The observed reduction in platelets was essentially equal to the reduction in platelets predicted if patients had received carhoplatin alone. Subsequently, a second cohort of 20 evaluable patients with NSCLC received the full calculated dose of carboplatin and etoposide (51 evaluable courses). There was a linear relationship between observed (0) and predicted (p) reductions in platelets. With full-dose carboplatin in combination with etoposide, there was a significantly greater reduction in platelets, and lower platelet nadir. Among 34 evaluable patients (80 courses) there was one complete response (CR) and four partial responses (PRs) for an overall response rate of 15% (90% confidence f 9%). The median duration of survival for responders was 336+ days and for nonresponders was 204+ days. Therapy was well tolerated. This study, in addition, supports our concept of individualized dosing of carboplatin and the underlying pharmacokinetic/pharmacodynamic relationships and represents an interesting pharmacodynamic and quantitative approach to studying potential drug-drug interactions and detining appropriate dosages for combination chemotherapy.

Phase II study of idarubicin in extensive-disease non-small-cell lung cancer Umsawasdi T, Holoye PY, Jeffries D, Cat? DT. Department of Medical Oncology, The UniversityofTexasM.D.AndersonCancerCenter,1515 Holcombe Boulevard. Houston. 7X 77030. Am J Clin Oncol, Cancer