Abstracts/ Lung Cancer 10 (1994) 395-430 423

Although the role of MVP in the treatment of advanced NSCLC is unclear, use of mitomycin-cootainiog regimens as part of a multidisciplinary approach to stage IIIA NSCLC has yielded high response rates and has successfully downstaged patients prior to surgery. Random&d clinical trials will be required to validate these. tindiigs, but the focus of future. research should be on discovering new agents with greater activity and on developing new approaches wherein thw agents can be delivered with maximum efficacy and minimum toxtcity.

Effect of suramin treatment on mesothelioma and other lung cancer derived cell lines Morocz IA, Lauber B, Schmitter D. Stahel RA. Division of Oncology. Dept. of Medicine, Vniwrsiry Hospital, CH-SO!Jl Z&rich. Eur Respir Rev 1993:3:213-S.

Pleural malignantmesothetiomaisrelativelyresistanttoconventioaal therapies. Summin has been shown to inhibit growth of certain solid N~OUIX. In the search for new treatment approaches for lung Nmours, we investigated the in vitro effect of suramin on deoxyribonucleic acid (DN~)a~~dp~oteinsyntheaisonsix mesotheliomacell linesandavariety of small-cell lung cancer (SCLC) andnon-SCLC cell lines, as well as on normal lung libroblasts and immortalized mesothelial and bronchial epithelial s. The affect ofsuramin was tested at concentrations which are tolerated in vivo (up to 300 g-ml”). Observationa over 8 days showed a considerable dose-dependent decrease of ‘H-thymidioe incorporation (3 I-9656). whilst ‘H-leucine incorporation remained unaffected, suggesting a cytostatic and not a cytotoxic effect. All of the cell lines tested, including the non-Nmour cells, showed a similar response pattern, with the exception of the adenocarcmoma cell line Al25, for which DNA synthesiswas stimulated in the presence of suramin. Thus, sunmin (at clinically tolerable coaceotntioos) inhibits the growth of mesothelioma to the same degree as other lungderived cell lines.

The use uf nuclear DNA content to monitor the chemosensitivity of hwnan non-small-cell-lung (NSCLC) and colorectal cancers xenografted onto nude mice Kruczynski A, Jannot M-C, Astruc J, Chasottes E, Limouzy A, Kiss R. Div. Cancerologie Experimetuale I, Cenrre de Recherchc Pierre F&e. 17AvenueJean Moulin, 81106 Casrres Ceda. Int J Gncoll993;2:593- 9.

The chemosensitivity of human lung and colorectal Nmours graBed onto nude mice was asses& at the individual Nmour-besring mouse level. The results show that various pieces of a given Nmour grafted onto a number of animals exhibit different profiles of sensitivity to the same chemothempy. We used the nuclear DNA content to subtype the clonal tumour heterogeneity of these models. This monitoring was period by means of the digital cell image snalysis of Feulgen-stained nuclei. The data show that the nuclear DNA content of human lung and colorectal models varies markedly not only over serial transplantations onto animals on the one hand, but also within one and the same xenografted tumour during its spontaneous growth on the other. Such nuclear DNA content variations might explain the variability of the chemosensitivity within a given human xenogmft model.

Phase II study of a 72-h concurrent continuous infusion of cisplatin and etoposide in advanced non-small-cell lung cancer Saito H. Shimokata K, Yamamoto M, S&a H. Sakai S, Saito H. 1st Depanmetu of brernal Medicine. Nagow Vniwrsity. S&ooiof Medicine, 65 Tsurumoi. Show&u. Nagoya 466. Cancer Chemother Pharmacol 1993;32: 134-6.

We conducted a phase II study to evaluate the antitumor activity and

safety of concurrent continuous iafusioa of cisplatin sad etoposide in advanced non-small-cell lung csncer (NSLCL). Cisplatin (30 mglm’ daily) and etoposide (80 mg/mr daily) were given as a 24-h continuous infusion for 72 h to 48 patients with previously untreated advanced NSCLC. Of the 46 evaluable patienta, 9 achieved a partial response, for an overall response rate of 20% (95% confidence interval, 9.4% 33.9%). The median duration of response was 23 weeks. The median duration of survival for all patients was 34.4 weeks. The major toxicity was hematologic. Leukopenia (WHO grade 3) was observed in 22 patients (48%) and thrombocytopenia (WHO grade 3), in 13 patients (28%). In all, 20 patients (43%) experienced severe anemia (WHO grade 3). Non-hematologic activity mainly consisted of moderate to severe alopecia in 33 patients (72%) and moderate to severe nausea and vomiting in 25 patients (54%). No significant nephrotoxicity was seen. We conclude that a 72-h concurrent continuous infusion ofcispiatin and etoposide does not appear to be active against advanced NSCLC.

Marked reduction of type I kerdtin (K14) in cisplatin-resistant human lung squamous+ucinoma cell lines Katabami M. Fujita H, Honke K, Makita A, Akita H, Miyamoto H et al. LaboratoryofMolecular Genetiicz. Cancerlnrtitute, Hokkaido Univ. School of Medicine, Kita- Nishi-7. Kira-ku, Sapporo 060, Biochem Pbarmacol 1993;45:1703-10.

We have established hvo cisplatin-resistant human lung squamous- carcinoma cell lines. PClO-B3 and PCIO-Es. from their original cell line PClO. To discover which proteins are associated with cisplatin resistance, we carried out a twodimensional gel electrophoresis to analyze differences in protein alteration between PClO. PCIO-B3 and PClO-ES. A protein spot M(r) 50 kDa, pl5.3, was reduced markedly and a spot M(r) 50 kDa, ~14.9 was increased when PClO-B3 and PCIO- ES were compared with PCIO. A spot M(r) 58 kDa, ~15.8 newly appeared only in PCIO-Es. Cell fractionation showed that the M(r) 50 kDa, p15.3 (~50-5.3) and the M(r) 50 kDa. ~14.9 fell within the nuclear fraction, while the M(r) 58 kDa, ~15.8 was found among the cytosol and microsomal fractions. Microsequencing atier in situ digestion of the dramatically reduced spot ~50-5.3 revealed that it was identical to 50 kDa. type I keratin (K14). Moreover, a retinoic acid-mediated K14 reductionwaaconcomitantwitha4.0-foldincreasrincisplatinresistance in PCIO. Our report is the first to suggest the possible association of marked K14 reduction and cisplatin resistance in PClO-B3 and PClO- E5.

Phase II study of carhoplatin and adriamycin as second line chtmotherapy in small cell lung cancer Falk SJ, Maughan TS, Laurence VM, Lament A, Boote D, Ford JM et al. MRC Unit. VniversityDeprof ClinicaiOncology, MRCCenrer, Hills Road, Cambridge CB2 2QH. Clin ollcol (GBR) 1993;5:85-8.

A total of25patientswithsmallcell lungcancer(SCLC) weretreated with carboplatin and Adriamycin (CA) following symptomatic relapse after initial therapy, or because of static or progressive disease during primary treatment. Nine patients had disease within the thorax, and 16 had extensive metastases at relapse. The overall response rate to CA was 64% (20% complete response: CR; 44% partial response: PR). Survial from presentation in 22 of the patients who have died was 6-36 months (median 13 months). and the median survival from the commencement of CA was 23 weeks (range 1 week-l 1.5 months). The duration of CR was4-8 months, and of PR 2-7 months. Hospital admission was required following 12% of cycles for management of the complications of treatment. The increasing use of tint line regimens of short duration

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