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Seven small,- (SCLC) and four non-small-cell (NSCLC) lung cancer cell lines were used to examine the in vitro cof cytotoxic drugs such as (aS(la_,86,8a_,8b_))-8-((aminocarbonyl)oxy)metbyl)-4,8a-di- methoxy-l,la,2,8,8a,8b-hexahydro-7-hydroxy-5-methyl-6-nitro- soaziri no(2’,3’: 3,4)-pyrrolo-(1,2-a)indole (RM-49) and 1 I-acetyl-l- carboxymethyl-4-formyl- 14oxa- 1 ,l I-diazetetracyclo(7.4.1.0 2~‘,010~‘2)tetradeca-2-4-6-trien-6,9-diyl-di acetate (FK973). In vitro cy- totoxicities of RM-49 and FK973 were compared with those of mitomy- tin C (MMC), cisplatin (CDDP), carboplatin (CBDCA), etoposide (VP16), adriamycin (ADM) and vindesin (VDS). Drug sensitivity was determined using a tetrazolium (MMT)-based assay. Average IC, values of these two drugs were not statistically different compared with that of MMC, although FK973 showed strong antitumor activity against SCLC cell lines such as LT3, N857, and H69 at the same concentration. The predicted peak plasma concentration (predicted PPC) calculated by the formula proposed by Scheithauer, log (predicted PPC) = -0.788 + (0.755 x log(LD,d),andrelativeantitumoractivity,RAA~PC/IC,),of RM-49 were higher than those of other drugs such as MMC, CDDP, CBDCA, and ADM against SCLC cell lines (P _ 0.05), and those of FK973 were also higher than those of other drugs such as MMC, CDDP, CBDCA, and ADM against SCLC cell lines (P _ 0.05). Based on these promising in vitro studies, the clinical trials of RM-49 and FK973 were warranted.

Phase I-II study of cisplatin, VP-16, MGBG, mitomycin, and vinblastine with radiation therapy for non-small-cell lung cancer. Christian ES, Schreeder M, Salter MM, Stephens SB, Carpenter JT Jr, Wheeler RH. Division of HemarologylOncology. Department of Medi- cine, University of Alabama Medical Center, Birmingham, AL 35294. Am J Clin Oncol, Cancer Clin Trials 1988;11:502-5.

Nineteen patients with locoregional non-small-cell lung cancer (NSCLC) were treated with two courses of cisplatin/VP-16/MGBG, followed by involved field radiotherapy and, subsequently, the same chemotherapy alternating with mitomycin-C/vinblastine. Five of 17 patients obtained a response (CR + PR) after induction chemotherapy. Following radiotherapy, an additional two patients responded. The median survival was7.5 months, with thetwolongest survivorsat30and 32 months. Hematologic toxicity was severe, with two deaths from scverencutropenia. Renal andgasuointestinal toxicities were moderate. This program of aggressive therapy did not increase tbe response rate or median survival compared with those of comparable patients treated in recent trials usrng radiotherapy alone or combined radiotherapy plus chemotherapy.

Etoposide (VP-16) and cytosine arabinoside in the treatment of relapsed small-cell lung cancer. Margolin K, Akman S, Can B, Leong L, Doroshow J. Departmenr of Medical Oncology, City of Ijope National Medical Center, Duarte, CA 91010. Am J Clin Oncol, Cancer Clin Trials 1988;11:499-501.

Seventeen patients with small-cell lung cancer refractory to combi- nation chemotherapy were entered in a study of VP-16 and infusional Ara-C. All patients were cvaluablc for response and I4 were evaluable for toxicity (three deaths that occurred after the first cycle of therapy were due to progressive tumor, and toxicity could not be evaluated in these three patients). Ara-C was given as a continuous intravenous infusion of 45 mg/m2/day for 72 h; VP-16 was given as three daily intravenous bolus doses of 50 mg/m2at hours 12,36, and 50 of the 72- h Ara-C infusion. Because of excessive myelotoxicity in the first six patients, the last 11 patients began treatment at a lower dose of Ara-C, 25 mg/m*/day. Six of 17 patients had previously been exposed to VP-16 as part of their initial chemotherapy regimen. The 17 patients received 32 cycles of therapy. Myelotoxicity was severe, with nadir granulocyte counts <500/*1 or platclct counts <30,000/*1 in four treatment cycles

(including two at the lower Ara-C dose). No patient experienced an objective response to this therapy. We conclude that the combination of VP- 16 and infusional Ara-C at these doses is excessively toxic and does not warrant further investigation in refractory small-cell lung cancer.

Chemotherapy of lung cancer. Drings P. Abteilung Innere Mddizin, Onkologie der Thoraxklinik Hei- delberg-Rohrbach &r LVA Baden, D-6900 Heidelberg I. Prax Klin Pneumol 1988;42(Spec Iss 1):340-3.

Since small-cell bronchial carcinoma must usually be considered a systemic disease, chemotherapy is the predominant form of treatment of this lesion. Polychemotherapy employing two or more cytostatic agents is superior to ‘mono-chemotherapy’. Objectively measurable remis- sions, including 40%-50% complete remission in the limited disease stage, are obtained in between 70% and 90% of the patients. This leads to a median survival rate within the overall group of patients of 12 months. In the case of complete remission, average survival increases to between 15 and 20 months. Five to ten per cent of all patients survive for 2 years and longer, with no recurrent disease, and can be considered to be potentially healed. In the stage of extensive disease, the percentage of complete remission is still 20%. with median survival of 7 to 11 months.ln thecaseofnon-small-cellcarcinomas,chemotherapy. which is usually administered in the form of polychemotherapy, has only a palliative intent. It leads to remission rates of 25%-45%, including complete remissions in about 5%. A reliable demonstration of the prolongation of life by chemotherapy has, so far, not been provided. For this reason, the establishment of the indication must be particularly strict. The value of adjuvant or neo-adjuvant chemotherapy has, todate, not been demonstrated unequivocally in any clinical study.

Development of drug resistance in a human epidermoid lung carci- noma xenograft line. Mattem J, Bak M Jr. Hoever KH, Volm M. Insrirure of Experimental Pathology. German Cancer Research Center, D-6900 Heidelberg. Br J Cancer 1988;58:30-3.

The development of resistance to vincristine, actinomycin D and cisplatin has been examined in a human epidermoid lung carcinoma xenograft line (HXL 55) growing in nude mice. Treatment of HKL 55 with I mg kg-’ vincristine or 0.5 mg kg-’ actinomycin D once in each in vivo passage resulted in a rapid reduction in tumour responsiveness to these drugs. A partial resistance was already acquired at the 2nd transplant generation. In contrast, a gradual decrease in therapeutic response was observed with 10 mg kg-’ cisplatin. Irradiation with a local dose of 10 Gy induced no resistance. The three induced drug-resistant sublines were characterized in terms of the time course of development of resistance, the degree of induced resistance, cross-resistance, growth rate and stability of the phenotype.

Chemosensitivity testing of human lung cancer cell lines using the MTT assay. Carmichael J, Mitchell JB, DeGraff WG et al. NCI-Navy Medical Oncology Branch, National Cancer Institute and Naval Hospital. Be- thesda, MD 20814. Br J Cancer 1988:57:540-7.

Thirty human lung cancer cell lines were tested for chemosensitivity using the semi-automated, non-clonogenic MTT assay. The tumourcell lines came from three major categories of patients: untreated small cell lung cancer (SCLC); SCLC relapsing on chemotherapy; and non-SCLC predominantly from untreated patients. From these data IC, values were derived for each drug in each cell line. While some inter- experimentalvariability wasobserved,therankorderofchemosensitiv- ity of each cell line within this panel was significantly correlated between experiments. These results show that tumourcell lines derived