Abstracts/Lung Cancer 12 (1995) 265-329

Cnrboplatin and etoposide in extensive small cell lung cancer Viren M, Liippo K, Ojala A, Hellc L, Hinkka S, Huovinen R et al. Dept. Radiotherapy andOnco/ogv. Kuopio UniwrsilyHospital, J?O.B. 1777, SF-70211 Kuopio. Acta Oncol 1994,33:921-5.

The combination of cartoplatin and ctoposide was evrduatcd in 61 previously untmtcd patients with extensive small cell lung cancer, Treatment was given at four-week intervals with 450 mpiml of carboplatin intravenously (i,v,) on day I and etoposidc 100 mp/m’ i.v. on days l-3. The rcsponsc was complete in 5 (9%) and partial in 28 (50%) of the 56 cvaluablc patients (overall response rate 59%). The median time to pmgrcssion atlcr response as well as the median survival time in all evaluablc patients was 4.6 months. WHO grade 3 and 4 lcukopcnia end thrombocytopenia occurred in 8% and 11% of the courses rCSpcC6Vely. TWO trcatmcnt-rclatal deaths were registered. The combination of carboplatin and ctoposidc used in the present tidy produced acceptable rcsponsc rate and toxicity, but duration of response and median survival wcrc shorter than expected from earlier studies.

Symptomatic, stpge W nun-small-cell lung caocer (NSCLC): Response, toxicity, paformaace status change and symptom relief In patients treated with cisplatin, tiblastine and mitomycM TummarelloD,Graziano F,Isidori P,CcllerinoR.Deporlntotro~edica/Oncol~~, Ospedale di Torrette, lJmiwrsi@ ofiincona. I-60020 Ancona. Cancer Chemother Pharmacol 1995;35:249-53.

In II series of 46 symptomatic patients with metastatic, stage rV, non-small- cell lung cancer (NSCLC), wc used a three-drug combination with cisplatin (120 mglm’). vinbladinc (6 mglm’) and mitomycin-C (6 mglm’) (PVM), repeated every 3 weeks. AtIer two courses, we observed that nc.nc of the patients had achieved a complete response; 33% (15146) had partial response (95% confidence limits: 19.2-46.8); 39% (18/46), stable disease and 28% (13/46), progressive disease. Median response duration was 14.0 weeks (range, 4-36.7), median time to progression 22.4 weeks (range, 74.4). and median survival time 26.4 weeks (range, l-103). WHO grade II&IV my&toxicity occurred in 15.2% ofthc courses administcrcd, affecting 39.5% of patients, and severe nephrotoxicity was observed in 9.3% of patients. No toxic death occurred. The post-treatment KPS score incrcascd in 7 patients with partial response (47%). 4 with stable disease (22%) and 1 with progressive disease (8%.), while it decreased in 3 patients with partial response (20%), 3 with stable dixasc (17%) and IO with progressive discasc (77%). In all, KPS increased in 12146 casts (26%). However, no statistically signitieant difference was observed when the KPS score before and after treatment was compared in the total group of patients or when it was compared in responders and in non-responders. AtIer chemotherapy, there was complete disappearance of at least one symptom in 27.1% of cases and improvement in 27.1%. Overall, major symptom control occurred in 54.3% of casts, with a median palliation time lasting 10 weeks (range, 4-32). Patients with partial remission and stable disease achieved symptomatic palliation in 90% and 55.5% of cases, respectively. When we compared the palliation rate between responders and non-responders, a significant difference was notcd (Chi-square test: P Ca.05). Although our schedule did not produce a higher objective response r&c and the KPS score was not significantly improved, the symptom palliation appeared worthwhile considering the highly unfavourable prognosis ofthe patients investigated.

IO vivo screening models of cisplatia-resistant human hmg cancer cell lines using SCID mice Hcikc Y, Takahashi M, Ohira T, Arioka H, Funayama Y, Nishio K et al. Pharmacology Division. National Cancer Center Res. Inst.. Tmkij S-I-I. Chuo- hr. T&a 104. Cancer Chemother Phsmwol 1995;35: 2004.

In viva screening models of II cisplatin (CDDP>rcsistant human small-cell lung cancer cell (SCLC) line, H69/CDDP, and a non-small-cell lung cancer fell (NSCLC) line. PC-141CDDP. were evaluated. The transplantability of the tumor xenografts to SCID miec was more than 90%. Tumor xenografts of H69ICDDP and PC-14ICDDP showed CDDP resistance during in viva treatment. The novel anticancer agent 254-S showed only a partial cffcet on the growth of H69/CDDP and PC-14/CDDP while ormaplatin showed no cross resistance to CDDP. The in viva results comlated well with the results of the in vitro MTT assay. In this in viva sensitivity test, H69lCDDP and PC-14ICDDP wcrc more sensitive to ormaplatin than its parental cell lines. In viva sensitivity testing using SCID mice bearing trsnsplantcd CDDP-resistant humors was shown to bc useful for evaluating the effects of new anti-cancer drugs. especially those that might cwcrcomc CDDP resistance.

Results of a clinical multicentric randomized pbase II study of non- small cell lung cancer treated with vinorelbiae-cisplatin versus vioorelbine alone Lorusso V, Peuclla G, Catino Ahi, Guida M, Scoditti S, Lorcnzo R et al. Medical Oncology Divtsion. Oncology Instimte. b Amend& 209, Bari 70126. Int J Oncol 1995;6:65-8.

From July 1992 to December 1993, 62 patients with non-small cell lung cancer (NSCLC) wcrc admitted to a multicentric randomized study. The patients were treated with vinorclbinc (V) alone at a dose of 25 mg/m%.v. weekly or with V at a dose of 25 mg/m*/i.v. on day 1 and 8 plus cisplatin at II dose of 80 mglm’ii.v. on day 1 ewy 3-4 weeks (VP). An objective response was observed in 42% of patients treated with VP versus 12.5% of those treated with vinorelbine alone (p = 0.038). Them was no significant differcnec in the median survival duration behucen the two groups (38 versus 30 weeks for VP and V, respectively).

Toxicity was tolerable but more swcrc in the VP regimen. These data suggest that v is an active agent in NSCLC and that the VP regimen may yield results comparable to other cispletin combinations for treatment of these tumors.

Inbaled recombinant intetfernn gamma in patients with lung cancer: Pharmacokinetics and effects on chemilumiaescence responses of ahdar macmphagea and peripheral blood neutropbils and niono=cw Halmc M, Maasilta P, Rcpo H, Ristola M, Taskinen E, Mattson K et al. Haartmaninkatu 4, SF-00290 HeLrinki. Jnt JRadiat Oncol Biol Phys 1995;3 1:93- 101.

Purpose: A Phase I trial was conducted to investigate clinical toxicity, pharmacokinetics, and chemilumincsccncc (CL) responses of alveolar macrophagcs (AM) and peripheral blood ncutrophils and monocytcs afier inhalation of recombinant interferon (I EN)-pmma. Methods and Moteti&: Eight patienti with lung c.mcer inhaled r lFN-gamma as single doses of 0.1, 0.2,0.6, 1.8, or 5.4 mg. Bronchoalveolar Iwage was performed three times, 21 h before as well as 3 and 27 h after inhalation. Resdts: Inkrfcron- gamma was detectable in bmnchoalveolar lavage fluid (BALF) samples taken 3 h after inhalation in doses of 0.6 mg. Before inhalation, AM in four out of seven patients studied showed vigorous lucigenin-znhanccd CL responses to N- formyl- mcthionyl-leucyi-phcnylalanine and opsanixd zymosan particles. Furthermore, the rcsponscs were markedly increased 3 h at?er inhalation. In three out of swcn patients, AM in the pr&eatment BALF se+mples showed low or no CL responses, and the responses did not increase after inhalation oflFN-gamma, suggesting that the patients wen ancrgic. P&inhalation CL rcsponscs did not correlate with the dose of IFN-gamma inhaled. Circulating IFN-gamma was detected in one patient receiving the highest dose. No changea rcfcrablc to IFN-gamma inhalation wcrc found in the CL responsea of blood ncutrophils and monocytes. During the 24 h follow-up, two patients developed transient fever-reactions. Conclusions: The findings suggest that inhalation may provide a way to increase alveolar eone-entretions of IFN-gamma and to augment respiratory burst capacity of AM without any major side cffccts. This approach may have clinical implications for the treatment of tllmors and infections of the respiratory tract.

Comp~lrtiwrtivityotluvetbine,ap~lbine+cisplntin,~odvi~de~iw+ cisplatin io the therapy ufunresectable non small cell lung carcinoma. Results of a multicentric European randomized trial including 612 patients G~nzala Lade JL, Albcrola V, Lianes P, Panizo A, Carrato A, Munoz Quintana A et al. Servicio de Oncologic Medico, Hospital Uniwsirario Son Carlo*, 0 Martin Lngos, dn. 28040 Madrid. Rev Clin Esp 1994;194:953-9.

The results are reported of three chemotherapy schedules in a multicentric, international, randomized trial of the therapy of unresectablc non small ~11 lung carcinoma which includetive for its antitumor effects or maintaining patients quality of Ii&.

Treatment of Non-Small cell lung cancer w3tb ifosfamide (IFO) + 4’- Epindriunyein~~+plrtinua~L++EPI:AGE~~~~~dy Bmcato N, B~no ME Araujo CE, Cervellino JC, Pirisi C, TemperIcy G et al. ticologv Unit Hospital. Hospital B. Housmy, PO Box 69 - SK. 24, 1424 Buenos Aiies. Oncology (Swikcrland) 1995;52:24-3 I.

203 patients with inopcrablc non-small cell lung cancer (NSCLC) were randomized to rcceivc ifosfamidc (IFO) 2.5 s/m’ days 1-2 + cpirubicin (EPI)