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100 mg/m2 teniposide. Although the number of patients is small and they were not randomly assigned to the two different teniposide doses, it appears that higher dose of tenoposide determined a greater degree of myelotoxicity, and also a higher response rate.

Prevalence of cytostatic+resistant lung tumour among smokers Volm M. Mattcm I, Samsel B. lnsriruffur Experimenrelle Parhologie, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, W- 6900 Heidelberg. Dtsch Med Wochenschrl991;116:1303-6.

The resistance of tumours against doxorubicin was determined in vitro and compared with their smoking habits in 94 patients (81 males and 13 females; mean age 59 [38-761 years) with non-small-cell lung tumour. Among nonsmokers (n = 22) 11 tumours were resistant and 11 sensitive, while among smokers (n = 72) 57 (79%) were resistant and only 15 (2 1%) sensitive to doxorubicin. P-glycoprotein was measured immunohistochemically and with the monoclonal antibody JSB-1 in order to test whether there is a relationship between the prevalence of resistant tumours among smokers and the expression of P-glycoprotein. Among 22 nonsmokers only two tumours (9%) were P-glycoprotein positive, but among 72 smokers, 42 tumours (58%) were positive (P < O.OCOl). Thus, the increased amount of resistant non-small-cell lung tumours in smokers can be explained partially by an increased expres- sion of P-glycoprotein.

Phase I study of weekly intravenous infusions of CPT-11, a new derivative of camptothecin, in the treatment of advanced non- small-cell lung cancer Negoro S. Fukuoka M. Masuda N. Takada M. Kusunoki Y. Matsui K et al. Department of Internal Medicine, Osaka Prefecrwal Habikino Hospital, 3-7-I Habikino, Habikino, Osaka 583. J Natl Cancer Inst 1991;83:1164-8.

7-Ethyl-10-[4-(1-piperidino)-l-piperidino]carbonyloxy-campa the- tin (CPT-I 1) is a novel camptothecin derivative that has been selected for clinical evaluation because of its broad spectrum of anti-tumor activity in animal models and its unique inhibitory effects on mammal- ian DNA topoisomerase I. Seventeen patients with advanced non- small-cell lung cancer were treated with CPT-I 1 at weekly dose levels ranging from 50 to 150 mg/m’. At least three weekly doses were given to ah patients except four, and a total of 74 weekly doses were given to the 17 patients. The dose-limiting toxic effects were myelosuppression (predominantly leukopenia) and unpredictable diarrhea. Gastrointesti- nal toxic effects were severe and not well conuolled by standard therapy m some patients. Interpatient variability of toxic effects was substantial (including two deaths) and did not correlate with the pharmacokinetic parameters of CPT11 and ‘I-ethyl-lo-hydroxycamptothecin, its major metabolite. Two previously untreated patients, who received doses of 100 and 125 mg/m2, had partial responses lasting 3.2 and 4.0 months, respectively. The maximum tolerated dose on this schedule was 100 mg/m’, which wealsorecommendasastartingdoseforphaseI1 studies. This schedule appears toallow a CPI-I 1 dose intensity which is double the dose intensity possible on a once-a-month schedule. However, careful supervision to assess gastrointestinal toxic effects and myelo- suppression is indispensable because of wide individual differences in drug tolerance.

tolerated, with 24% or less grade 3 or greater toxicities of all types. One toxic death was attributed to fluid overload. The response rate, partial and complete, was 43% (95% confidence interval, 27% to 63%) and median survival was 13.8 months for patients with stage BIB disease. Response rates refer to the chemotherapy response. For patients with stage IV disease, the response rate was 34% (95% confidence interval, 24% to 47%). and median survival was 6.2 months. On this regimen, stable-disease patients with stage IV disease had survivals at least equal to responders.

Phase If studies of 4’-iodo-4’-deoxydoxorubicin iu advanced non- small ceU lung, colon and breast cancers Sessa C, Calabresi F. CavaIli F, Cemy T, Liati P. Skovsgaard T et al. Servirio Oncologico, Ospedale San Giovanni, 6SOO Bellinzona. Ann Oncol 1991;2:727-31.

The new anthracycline analogue, 4’-iodo-4’-deoxydoxorubicitt (I- IXX), was administered at 70 mg/m’ as first chemotherapy in 61 patients with advanced NSCL (19). colon (20) and breast cancers (22). Treatment was repeated every 3 weeks; the dose was decreased to 60 mg/m2(19% ofthecycles)orincreasedto 80mg/m2(17% oftbecycles) according to the grattulocyte count nadir. Partial responses were ob- served in 6% of the patients with NSCL, in 5.5% of those with colon and in 10% of those with breast cancers. The main toxicity was a selective granulocytopenia characterized by a duration of about 1 week, and a high inter-patient variability. Non-haematological toxicities were mdd. The negative results obtained in breast cancer might be related to the dose administered. Further studies in this turnout type should be performed with a more aggressive schedule.

Phase f/II clinical trial of didemnin B in non-small-cell lung cancer: Neuromuscular toxicity is dose-limiting Shin DM, Holoye PY, Murphy WK. Forman A, Papasozomenos SC, Hong WK. Raber M. Depanmenr of Medical Oncology. UniversiQ of Texas MD. Anderson Cancer Center, IS15 Holcombe Boulevard, Houston, TX 77030. Cancer Chemother Pharmacol 1991;29:145-9.

Didemnin B (NSC 325319). a cyclic depsipeptide isolated from a Caribbean tunicate, exhibits potent preclinical antitumor activity. In previous phase I studies, 3.47 mg/m* was the maximally tolerated dose, with nausea and vomiting being the dose-limiting toxicity. The drug was given in a single bolus infusion over 30 mitt every 28 days. In the current study, 30 patients presenting with previously treated non-small- cell lung cancer (NSCLC) received 46 courses of the drug at doses ranging from 3.47 to 9.1 mg/m’. Neuromuscular toxicity was dose- limiting. Nausea and vomiting appeared to be correlated with dose levels and were ameliorated by a combination of antiemetics including dexamethasone. Other side effects included a mild rise in hepatic enzymes and an allergic reaction that was preventable by the addition of corticosteroids to the premeditation regimen. In all, 2 minor re- sponses were seen among 24 evaluable patients. Because neuromuxu- lat toxicity is dose-limiting, we recommend that routine measurements of creatine kinase and aldolase, a careful neurologic evaluation, and electromyography and muscle biopsy (if indicated) be incorporated into phase II trials. The recommended dose for phase II studies using a single bolus schedule is 6.3 mg/m2, followmg the premeditation of patieuts with antiemetics.

advanfed or metastatic non-smatl-cell lung cancer: A Mid-Attantic Oncology Program Study Heim W, Wampler GL, Lokich JJ, Brereton HD, Scialla SJ, LaLuna F et al. Mid-Atlanfic Oncology Program, 1511 KSr NW, Washington. DC X405. J Clin 0x01 1991;9:2162-6.

A combination of cisplatin administered as a 24-hour infusion and fluoromacil administered as a 5&y infusion was used to treat 97 patients with non-small-cell lung (NSCLC) cancer in a phase II trial. ThinypatientshadstageIIIBdisea.se;67patients,stageIVdisease(new international classification). Patients with stage IIIB disease also re- ceived tboracic radiation after chemotherapy. The regimen was well

SFluorouracil, etoposide, and cisplatin in the management of metastatic non-small cell lung cancer Flaherty L. Wozniak A. Redman B. Kraut M. Martmo S. Heilbrun L. Valdivieso M. Division ofHematology/Oncology, Wayne State Univer- sity/Harper-Grace Hospitals, P.O. Box 02188, Detroil. MI 48202. 0188. Cancer 1991;68:944-7.

Encouraging response rates have been reported in Stage III non-small cell lung cancer when 5-fluorouracil (5.FU), etoposide (VP-16). and cisplatin (F!ZD) have been combined with radiation therapy (RT)orRT and surgery. The current study evaluated the effectiveness of FED chemotherapy in 32 patients with metastatic non-small cell lung cancer.