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Abstracts/ Lung Cancer I1 (1994) 123-150 145
status and weight in responding patients. Larger- scale random&d trials of MIC are currently under way and, prelimimuy response data support the results of earlier studies. The ultimate role for chemotherapy in NSCLC will depend upon its impact on survival and quality of life. As yet neither havebeen evaluated thoroughly enough for any chemotherapy regimen to be regarded as standard treatment in this disease.
Chronic oral etoposide in small-cell lung cancer: Clinical and pharmaeokinetic results Sessa C, Zucchetti M, Toni V, Pagani 0, D’lucalci M, Gentili D et al. Depamnenf of Oncology, Osptxiale San Giovanni, Bellinzona. Ann Gncol 1993;4:553-8.
Aims: To evaluate antitumour activity, toxicity, pharmacokinetics, and the pharmacodynamic relationship with neutropenia of chronic oral etoposide (E) in patients @ts) with small-cell lung cancer (SCLC) previously untreated with chemotherapy. Parienrs andmethodr: Tweuty- seven (14 extensive-, I3 limited-stage) pts receiving 100 mg daily of oral E for 21 days every 4 weeks. CBC with differential repeated every week. E plasma levels determined by HPLC method (sensitivity limit: 0.1 g/ml) with evaluation during the first cycle of weekly 24-hour drug concentrations. Results: Among 25 evaluable pts, 60 96 (95 96 Cl: 39 I- 79%) overall response, 144 and 217 days of median PFS and survival. Dose-limitingnoacumulPtiveneutropeniaofhighinterpatientvariability. Linear reduction (30% per week) of absolute neutrophil counts (ANC) up to the 3rd week, recovering the following week. Risk factors for neutropenia (age, PS, serum creatinine and albumin) not identified. High inter-patient variability of 24-hour E plasms levels. A weak correlation between mean 24-hour E plasma levels and ANC nadir or relative decrease of ANC, but higher relative decrease of ANC in pts with 24-hour E plasma levels of > 0.32 g/ml. Conclusions: Chronic oral E is effective in SCLC pts previously untreated with chemotherapy. Careful hematological monitoring is essential to avoid severe myelosuppreasion. The degree of neutropenia might be related to the maintenance of a critical drug concentration level for a critical period of time.
Pilot study of cyclophosphamidedoxorubicin-vincristine- cisplatin- etoposide hybrid chemotherapy in small cell lung cancer Ohnoshi T, Hiraki S, Ueoka H, Kiura K, Kamei H, Horiguchi T et al. Second Department of Medicine, Okayama University Medical School, 2-5-l Shikata-cho, Okayama 700. Cancer 1993;72: 1597-1601.
Background. Small cell lung cancer (SCLC) is highly sensitive to chemotherapy. Despite the introduction of intensive combination chemotherapy, long-term disease-free survivors are still rare. The emergence of drug- resistant tumor cells during chemotherapy is presumed to be the major cause of poor outcome. Methods. A pilot Phase II study of hybrid chemotherapy for patients with SCLC was conducted between October 1986 and March 1988. Dose and schedule for each drug in the regimen were as follows: cyclophosphamide, 700 rng/n? intravenously (IV), day I; doxorubicin, 30 mglm2 IV, day 1; vincristine, 1.4 rng/r& IV, day 1; cisplatin, 60 mg/m? IV, day 8; and etoposide, 100 mglmr IV, days 8 and 9. Courses were repeated every 4 weeks for up to six cycles. Patients with limited disease (LD) received chest irradiation of 5000 cGy when a maximal response was achieved. Only patients with LD who achieved a complete response (CR) received prophylacticcranial irradiationof3OOOcGy. Results. Thirty-six patients were enrolled and fully evaluated for tumor response and toxicity. All 20 patients with LD responded to the regimen, and 14 (70%) of those achieved a CR. Of 16 patients with extensive disease (ED), 7 CR and 7 partial responses were noted, indicating an overall response rate of 88 96. The median survival time was 23.6 months for patients with LD
and 12.6 months for those with ED. Myelosuppression was the major toxicity, but it was generally well tolerated. Conclusions. These results indicate that the hybrid regimen is a highly active one for the treatment of patients with SCLC and warrants additional clinical trials.
A Phase II study of methotrexate, doxorubidn, cyclophos- phamide, and lomustine chemotherapy and lonidamine in ad- vanced non-small cell lung cancer Buccheri G, Ferrigno D, Ross0 A. via Repubblica IO/c, I-12018 Roccavicne (CN). Cancer 1993;72: 1564- 72.
Background. Combination chemotherapy with conventional anti- proliferative drugs is becoming the treatment of choice for patients with advanced non- small cell lung cancer (NSCLC), a good performance status, and no major clinical contraindications. Lonidamine (LND), a new drug with an innovative mechanism of action, might poteutiate anticancer activity, without increasing toxicity. hfcthodr. In a Phase II study, 46 patients with advanced NSCLC were assigned to receive chemotherapy with the methotrexate, doxorubicin (Adriamycin, Adria Laboratories, Columbus, OH), cyclophosphamide, and lomustine (MACC) regimen, as originally described, plus LND, 1.50 mg orally, three times per day. Treatment was continued until progression of disease, occurrence of unacceptable toxic effects, or refusal by the Patient (the median duration of MACC treatment was 6 weeks; 7 weeks for LND). Results. For the whole group of patients, actual dose intensities (Dl) of MACC and LND were 95% and 67% of those projected(medianvalues), respectively. TherewPsanegativecorrelation between duration of chemotherapy and the Dl of MACC reached in each patient. On the contrary, there was no correlation between the duration of treatment with LND and its Dl. The Dl of LND and MACC were not correlated with each other. ln all, seven objective responses (only partial responses) were observed. The overall median survival time was 42 weeks (confidence limits [CL], 20-52). The median survival length of patients receiving the full dose of LND (450 mg daily for at least 1 week) was 46 weeks (CL, 28-67) as compared with the median survival of 19 weeks (lower CL, 9 weeks) for the remaining patients: this difference was statistically significant (P < 0.05, Breslow teat). Toxic effects were as expected with the use of MACC. They were mainly gastrointestinal (any grade of toxicity occurring in 64% of the Patients), hematologic (anemia, 44% ; leukopenia, 36 I ; thrombocytopenia, 8 W), oral (2.5 W), renal (14 %), and cardiac (11%). There was only one treatment-related death, from myocardial infarction and neutropenic sepsis. Uncommon side effects, which were attributed to LND, were mild to moderate and reversible; they included myalgia (26 %), asthenia (15 %), testicle pain (ll%),vi~p~ble~cI%),andgastricintolerance(7%).Conc~ion~. MACC plus LND is a moderately active regimen in advanced NSCLC, with foreseeable and reversible toxic effecta of low-medium grade. Potential enhancements of antitumor activity and possible host survival benefits may be expected by the addition of LND to MACC, but a Phase Ill study must be performed to identify them.
Factors influencing response to second-line treatment with tenlposide (VM26) in patients with progressive small cell lung cancer (SCLC) Tummarello D, Graziano F, Giordani P, Cellerino R. Oncologia Medica, Ospedale Torretre, WOZO Ancona. Anticancer Res 1993;13: 1055-8.
Twenty-eight patients with small cell lung cancer (SCLC), I2 with limited (LD) and 16 with extensive (ED) disease, 22 of them relapsed to first-line treatment and 6 not responsive, were. treated with a single- agent second-line treatment consisting of ten&side (VM26) 60 mglm2, i.v. on days 1 to 5, every three weeks, until progression. After a minimum of two courses, we observed no complete response, 7 (LD/ED