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tin + lomustine. The hypothetical superiority of this regimen was based on data from experimental animal tumors suggesting potentialed effi- cacy of the three specific combinations. A mtal of 234 patients were included. and 113 vs 108 patients wereeligible. Median survival in bolh gmups was 48 weeks @ = 0.89). Complete remissions were observed in 36/101 and in 42/99 patienu evaluable for response. There was no signilicantdifferenceinresponseduration.A~restagingafter 18months ofcherolhaapy27patienu(l6%)and22padents(16%),respectively, were free of disease. Six patients, three in each arm, are. still alive, 8+ to 10.5+ years after diagnosis. Scheduled doses of the six agents were the same in the two regimens except for a 30% reduction of every second dose of cyclophosphamide in regimen B. Nevertheless. regimen B resuhed in signiticantly more leukopenic patients, septicemic epi- sode.s, and blood uansfusions, and the dosage of etoposide was more oftcn reduced in arm B lhan in arm A. The increased toxicity was not assccialed with improved Vestment results.

Cbemoseasitivity testing of small cell lung cancer using the MTT

-Y CamplingBG,Pym J,Baker HM,ColeSPC,LamY-M. OnrarioCancer Treatment andResearch Foundktion. Kingston Regional Cancer Centre, King St West. Kingston, Ont. K7L 2V7. Br J Cancer 1991;63:75-83.

A simple calorimetric lest, dic MlT assay, has been adapted for chemosensitivity testing of human small cell lung cancer cell lines, and fresh lumour samples. Optimal conditions for clinical chemosensitivity testing were determined using established SCLC lines. Nineteen differ- em chemotherapeutic agents were tested, and sixteen of them were found u) be cytotoxic in this assay system. The drug sensitivity of a panel of 16 SCLC cell lines was measured and compared. There were very little intraexperiment varialion, but the interexperiment variation was significant. Cell lines which were derived from patients who had IKN received chemotherapy at the lime the cell line was cstablisbed were more sensitive (to all but one of the drugs) than lines derived from treatedpalients.andtbediffere.nces werestatisticallysignificantfortwo of the drugs. Gne cell line, NCI-H209. which was derived from an umreated patient. stood out as being the most sensitive or among the most sensitive to all of the drugs tested. Another cell line, H69AR. which is a multidrug resistant subline of the cell line NCI-H69, was the mostresistam to many of the natural product drugs tested. Multiple drug chemosensitivity testing was performed on eight fresh turnour samples from SCLC patienls (live pleural effusions. one lymph node. and two primary turnours). It was possible to perform chemosensirivity lesting on all of the clinical samples in which sufficient tumour cells were available. The drug sensitivity of Ihe clinical samples was, in most cases, within the same range as for lhe cell lines. Since this assay is very rapid and simple LO perform, ic may have practical applications in clinical drug sensitivity testing of human mmours.

Circulating hematopoietic progenitors in patients with primary lung cancer Shimizu E, Mukai J-N, Takaue Y. Ogura T. Third Deparlmenl of internal Medicine, University of Tokoshima School of Medicine, 3- 18- 15 Kuramoto-cho, Tokushima 770. Jpn J Cancer Res 1990;81:1293-9.

The levels of circulaling hemalopoielic progenitors were measured in 28 patients with primary lung cancer. The average numbers of progenitors per millililer of blood were 33 (range O-360) for colony- forming unit-granulocyle macrophage (CFU-GM), 23 (range O- 140) for burst-formingunit-erylhmcyte(BFU-E),and4(rangeO-SO)forcolony- forming unit-mixed lineages (CFU-mix). No significant influence of age, sex. histological type, or clinical stage of the tumor on the progenitor levels was de&ted. After cytoreductive chemolherapy of lhepatientsby lrcalrnent with cisplarin plusetoposide,~becells showed 6- to SO-fold rebound overshoots, but no rebound was observed after ueatmem wilh cisplatin alone, cisplacin plus milomycin C or cisplatin plus vindesine plus mitomycin C, or in 4 of 5 patients treated with cyclophosphamide plus adriamycin plus vincrisdne. Peripheral blood hematopoietic progenitors should be useful as an abemative source of stem cells for lung cancer padena vcated with marrow ablative chemo- therapy.

Accelerated chemotherapy with or without GM-CSF for small cell lung cancer: A non-randomised pilot study Ardizzoni A. Sertoli MR. Corcione A, Pennucci MC, Baldini E, lntra E et al. Division ofPediatric Hematology-Oncology, Istittuo Scientifco G. Gaslini. Genova. Ear J Cancer 1990;26:93741.

Two series of five consecutive patients with small cell lung cancer were treated with an ‘accelerated’ chemotherapy regimen of cyclo- phosphamide-doxorubicin-vincristine (CAV) and cisplatin-etoposide (FE) alternated possibly every week. In the first group of patients (median age 49 years, range46-52) recombinant gramdocyte.e-macmph- age colony-stimulating factor (GM-CSF) was given as soon as grade IV leukopenia occurred, while in the second group (median age 59 years, 55-68) no growth factor was administered. The mean interval between chemotherapy courses and the mean duration of chemotherapy were 10 and 57 days, respectively, in tie patients supported with GM-CSF compared with 13 and 72 days in the control group. One GM-CSF treated patients was withdrawn after the third cycle because of severe toxicity. The mean while blood cell and platelet nadirs were 600 and 46OCO/plin Ihefirstgroupvs. 840and lOSOOO/pl in Ihecomrols.Overall chemotherapy dose-intensity was increased by two fold in the patients given GM-CSF compared with a 1.5 fold increase in the contml patients. In all cases, irrespective of their treatment. there was an impairedcolony formingcapacityofcirculatingandmarrow haemopoi- etic progenitor cells when grade IV leukopenia occurred, with recovery after the end of leukopenia. This pilot study suggesta that accelerated CAV/PE chemotherapy is feasible both with and without GM-CSF. Different GM-CSF schedules as well as combinations of different haemopoietic growth factors may further improve dose-intensity.

Experimental modelsof regional chemotherapy via the pulmonary artery using cisplatin Rauo GB, Esposito M, Vannozzi M, Fulco RA, Rovida S. Istitttto di Clinica Chirurgica la, Universita di Geneva, Viale Benedetto XV. 10, J-16132 Geneva. Reg Cancer Treat 1990,3:222-7.

The pharmacokinetics of cisplatin was investigated in pigs according 10 tbe infusion mute and administration modality. Twelve pigs were assigned to receive cisplalin (2.5 mglltg) via tie systemic vein, pulmo- nary artery, pulmonary artery with stop-flow, and pulmonary artery wilh stop-flow/outflow occlusion. Serial blood. lung parenchyma and mediastinal node &unples were obtained before, at completion of. and 5,15,30,60,120.180, and 240 min after infusion. Urine samples were collected 2 hand 2-4 h following drug administration. Specimens from thyroid. esophagus. heart, liver, spleen, adrenal gland, kidney and bone marrow were taken 4 h after treatment. Platinum concentrations in plasma, plasma ultratiltrate. erylhrocytes, tissues and urine were deter- mined by nameless atomic absorption spectroscopy. Pulmonary artery infusion, with or without stop-flow, yielded no significampharmacoki- netic advantage with respect m the systemic vein administration. In- stead, pulmonary artery infusion wilh stop-flow/oulflow occlusion

.? and lower syslemic plasma and tissue platinum levels.

Ifosfamide,cisplatin, vinblastine combination chemotherapy in the treatment of advanced non-small-cell lung cancer SaitoH,ShimokalaK.Yamamo~oM,SakaH.SakaiS.KawachiHetal. First Department ofMedicine, Nagoya Universiry School of Medicine. Tsurumai. Showa-ku, Nagoya 466. Cancer Chemother Pharmacol 1990;27:251-2.

A to~ll of 42 evaluable patients with previously untreated advanced non-small-cell lung cancer were treated with a combination of cisplatin @Omg/m’,day I).vinblasdne (5 mg/m’.days 1 and lS).andifosfamide (1.2g/m*,days l-3). lnall, 1 completeresponseand 15pardalresponses were obtained, for an overall response rate of 38% (95% confidence limits, 23.6%54.4%). The median duration of response was IS weeks. and the median overall survival was 56 weeks. Toxicity mainly con- sisted of moderate to severe alopecia in 28 patienls (67%). moderate to severe nausea and vomiting in 27 subjects (64%). and leukopenia comprising< 1,0001eukocytes/mm3in6cases(14%).1na11, 16patienU (38%) had microscopic hematuria (WHO grade I), but no hemorrhagic cystitis was documented. Although lhis three-drug combination ap-