148 Abstracts/Lung Cancer I2 (1995) 113-160

chemotherapy between CDDP + MS + UFT and UFT, in which wratively or relatively noncuratively resected patients were randomized The effects and validity of postoperative adjwant chemotherapy were evaloated in terms of the 3-year smvival rate as compared with those of operation only. 1) A satisfactory 3-year survival rate was obtained in both groups in which postoperative adjuvant chemotherapy was performed compared with the operation-only group. 2) Postoperative adjuvant chemotherapy was effective in stage IIIA, in cases of adenocarcinoma in which relatively curative surgery was performed. 3) Recurrence rates 3 years after surgery were lower with postoperative adjwant chemotherapy as compared with operation only. In parbcular recurrence was lowest in the m group. Thus, postoperative results were better in patients who received adjuvant chemotherapy. Postoperative adjwant chemotherapy using UFT alone was also effective.

Docet8xel (‘lhxotelr”) is active in am~+nall-cell lung can&: A phase II trial of tbe EORTC early clinical triala group (ECTG) Cemy T, Kaplan S, Pavlidis N, Schoffski P, Epelbamn R, Van Meerbeek Jet al. Institut~rMedizinische Onkologie, Inselspital, CH-3OIOBerne. Br J Cancer 1994;70:384-7. In a multicentre trial of the EORTC ECTG we have treated 43 non- pretreated patients with advanced non-small-cell lung cancer (NSCLC) with the new semisynthetic taxoid docetaxel (TsxotereR). Six patients were ineligible; of the 37 eligible patients, ten had prior radiotherapy and 18 prior surgety They received 100 mg me2 in 1 h i.v. every 3 weeks, usually in an outpatient setting. Prophylactic steroids, autihistaminics or antiemetics were not routinely given. *o patients were not evahtable because they withdrew from the stndy because of a hypersensitivity reaction after the second cycle. The main toxicity was neutropenia (80% of cycles), although infections were rare (4%). One patient died from sepsis during neutropenia. Hypersensitivity reactions necessitating interruption of docetaxel (Taxotere) infusions were found in only 10% of Cycles. The overall response rate was 23% with one complete response, and seven pattial responses, Stable disease was found in 16 patients. The median duration of response was 36 weeks, and the median survival of all patients was 11 months. Docetaxel (Taxoteres) is among the most active drugs for treatment of NSCLC.

Inhibition of grorstb of human small cell lung cancer by brnmo- criptine lshibashi M, Fujisawa M, Fume H, Ma&Y, Fukayama M, Yamaji T. Fourth Department OfMedicine, Teikyo University School ofMedicine, 74 Mizohokuchi, Takatsu-Ku, Kawasaki, Kanagawa 213. Cancer Res 1994;54:3442-6. Bromomiptine, a dopaminergic agonist, inhibited the growth of human small cell lung cancer (SCLC) implanted as tumor xenogra8.s in athymic nude mice; the effect was dose dependent. In mice bearing a SCLC with ectopic vasopressin production, plasma levels of human vasopressin-associated neurophysin decreased concomitantly. Electron microscopy of hunor tissues revealed marked degenemtive changes, including pyknosis, densely aggregated chromatin masses, and vacuolization of cytoplasm a&r bronmcriptine treatment. When a SCLC cell line, NCI-H69, was grown in semisolid medium, bromocriptine inhibited its clonal growth in a dose-related manner Coincubation with dopamine D, receptor antagonist, metoclopramide, or domperidone, completely blocked the inhibitory effect of bromocriptine. Receptor studies with a dopamine D, receptor ligand, [~z~l]iodosulpride. showed high affinity binding sites on the membranes of SCLC cells These reauhs indicate that SCLC cells ate enriched with dopamine D, receptors, which may mediate the growth-inhibitory effect of bromocriptine on SCLC. Dopaminergic agonists may be useful in the medical treatment of SCLC.

A Phase II trial of alpha-interfemn and 5-tluomuracii in patients with advanced carcinoid and islet cell tumors Saltz L, Kemeny N, Schwartz G, Kelsen D. MemorialSloan-Kettering Cancer Ctr., 1275 York Avenue, New York, NY 10021. Cancer 1994;74;Suppl: 95861. Background. 5-Fluoromacil (WU) has shown modeat single-agent activity in patients with carcinoid or islet cell tumors. Alpha interferon (a-IFN) has also shown modest single agent activity in these diseases, although biologic responses have been far more prevalent than have objective tumor regressions. The combination of a-JFN and 5-FU has demonstrated enhanced activity in several gastrointestinal malignancies. Methodr. ‘Dventy-one patients with advanced neuroendocrine tumors (14 with carcinoid tumors, 7 with islet cell carcinomas) were treated witha-IFNand5-FUinaPhaseUstmiy. 5-Fhtoroumcilwasadmimstered by intravenous bolus injection at an initial dose of 400 mg/mWay for 5 consecutive days. After a l-week break, 5-FU then was administered weekly by intravenous bohrs at a dose of 750 mg/m2. Alpha interferon administration was begun on Day 1 of 5-FU at a daily dose of 3 x lo6 U subcutaneously and continued for the duration of the trial. Results. of the 14 carcinoid patients with carcinoid tumors, 1 experienced a partial response (7%; 95% confidence interval [Cl] O-20%) that lasted for 6 months. Eight of the patients with carcinoid tumors achieved stable disease for a medianof months (range. 2-10 months). Gne ofthepatients with islet cell tumors (14%; 95% Cl O-39%) achieved a partial response that persisted after 8 months; 4 patients with islet cell tumors had stable disease for a median of 13 months (range, 4-27+ months). Even at this relatively low dose of a-IFN, 14 of 2 1 patients required a dose reduction in the a-IFN (13 for fatigue, 1 for ataxia). Three patients experienced myelosuppressionofgreaterthsnGmde3, andthree.patientshaddiarrhea of greater than Grade 3. One patient experienced dose-limiting hand-foot syndrome. Conclusions. These results suggest that the combination of 5-FU and a-IFN does not have any clear superiority over the individual agents alone; 5-FU appears to reduce patient tolerance of a-IFN when given on a daily schedule. Further investigations are needed to identify active agents in the treatment of neuroendocrine malignancies.

Vinorrlbine monocbemotberapy in non-small-cell lung cancer: Experience in patients with low performance status Masolti A, &mini G, Poggi R, Morandini G.C. PneumologvDivision, Ospedale Maggiom, ULSS 25, Verona. Monaldi Arch Chest Dis 1994;49: 197-200 The aim of this study was to investigate the activity and safety of vinorelbine in patients with low performance status. From March 1992 to June 1993 we studied 14 mttreated patients with Stage IV non-small- cell lung cancer (NSCLC) and a performance status’ lower than 70% of the Kamofsky score. Treatment was by means of an intravenous administration ofvino~bine (30 mg’m-r) repeated neekly. Gn the whole, the toxicity was mild. of 150 cycles administered, we observed 10 cases of Grade 3 leucopenia and 4 casea of Grade 4 leucopenia. A peripheral neurotoxicity (Grade 2-3) was reported in two patients. The objective msponseratewns36%partialreaponse. Gurdatasuggestthatvinorelbine could be an active and safe treatment for those patients who cannot receive polychemothetapyb of low performance status, andjustifv further larger studies comparing vinorelbine, either as a single agent or in combination, to other analogues or to assess ita efficacy in supportive cafe.

The role of chemotherapy in the treatment of stage III non-small- cell lung c.ancr mSCLC) Manegold C, Drings P. Abteilung Innere Medizin/Onkologie, Thoraxklinik. LVA Baden, Amalienstrawe 5, D-69126 Heidelberg Oukologie 1994;17:294-302. For the majority ofpatients in stage IJJ non-small lung cancer (NSCLC),