Abstracts/Lung Cancer 12 (1995) 265-329

Combination ofcisplatia and intelferooaZa (RoferoP-A) in patients withnoa-smallceU hmgcancer(TVSCLC).AoopenpbaseIImolticentre

study Keteja V Yap A. Roche International, Clinical Research Cerzter: Part Club des Tannerieq 4 Route de la Rivtm. 67382 Lingolsheim Ceder Eur J Cancer Part A Gcn Top 1995;31:35-40.

Prmlinical and preliminary clinical data suggested a potentiation of the cytotoxic activity of cisplatin (COOP) by intcrferona @N-a) in non-smell cell lung cancer (NSCLC). This open, non-randomised, phase lI shrdy was set up to detrrmine the response rate, duration of response, survival, safety and tolerability following treabncnt with the combination of recombinant IFNa2a and CDDP in NSCLC. 100 previously untreated patients with unrcsectable, measurable or evaluablc stage III/IV NSCLC were cnmllcd for treatment with a combination of IFN&2a (9 MIU three times weekly) end CDDP (IO0 m&m’ every 28 days). Patients were stratified awording to histology, i.e. squamous cell carcinoma versus non-squamous cell carcinoma. The planned maximum treatment duration was 6 months or until disease progression. Responding patients could be trcatcd with IFNu2a as maintenance for an additional 6 months. To bc cveloablc, the patients must have received at least 2 weeks of trcatmcnt with lFNu2a end at least one dose of CDDP. Them were 75% male and 25% fcmalc patients with a mcen ege of 59 years (range 34-74). An overall response rate of 33% (95% confidence interval (CL) = 2344) was achieved among the 84 cveluable patients. Then was one complete rcspondcr end 27 partial responders, while 32 patients had stable disuse. The duration of partial response rangcd from 3 to 12 months. The median survival was 6.4 (95% C.I. = 5.7-8) months. The response rate in patients with stage IIIa disease (45%) was significantly higher (I’ = 0.047) than in patients with stage N disease (22%). The median survival in psticnts with stage IIIa disease (9.3 months) was significantly longer (P = 0.025) then patients with either stage IIIb (6.3 months) or stage IV disease (6.2 months). The major forms of toxicity were gestmintcstinal and constitutional symptoms of mild to moderate severity. The main scverc adverse events (WHO grade 3-4) were nawca and vomiting (32%), anorexia (16%) end fcvcr (11%). The most frequent scvcrc hacmatological toxicitics (WHO grade 3-l) were ncutmpcnia (27%), anaemia (18%) and thrombocytopcnia (10%). 13 patients experienced WHO grade 34 renal toxicity. This study confirms the entitomour activity of the combination of IFNaZa and CDDP in NSCLC Futthcr study of this combination is warranted.

Symptom relief with MVP (mitomycin C, vinblastioe and cisplatin) chcmothcrapy in advanced non-small-cell long cancer Ellis PA, Smith IE, Hardy JR, Nicolson MC, Talbot DC, Ashley SE et al. Royal Marsden Hospital, Sutton. Suwey Sk42 5pI Br J Cancer 1995;7 11366-70.

The role of chcmothcrapy in the palliation of patients with advanced stage (IIIB and IV) non-small-cell lung cenccr (NSCLC) remains controversial. We have carried out a chemotherapy study cmphasising symptom relief, a topic not normally discussed in previous similar studies. A total of 120 patients with locally advanced or mctastatic non-small-cell lung cancer (NSCLC) were treated with a moderatedosc palliative chemotherapy rcgimcn consisting of mitomycin C 8 mg m’ t.v. on day 1 (alternate courses), vinblestine 6 mg m-’ i.v. on day 1 and cisplatin 50 mg rn.I i.v. on day I (MVP), rcpcating every 21 days for a maximum of six courses. Thirty-eight of 118 assessable patients (32%) achicvcd on objcctivc response. Paticnb with locally advanced disease (stage IIIB) had a significantly better response rate (52%) than those with metestatic discasc (25%) (P c 0.01). In 76 out of 110 (69%) patients, with tomour-related symptoms including 24 out of 31 patienta (78%) with locally advanced discasc, symptoms completely disappeared or substantially improved. In only 15 patients (14%) did symptoms progress during treatment, Symptomatic improvement was achieved after one coarse of chemotherapy in 61% and after two courses in 96% of responding patients. The schedule was well tolerated. Only 19% devclopcd WHO grade 3/4 nausea/vomiting, and only 3% developed significant alopecia. Other toxicities wcrc minimal. MST is a pragmatic inexpensive chemotherapy regimen that offers useful symptom palliation in patients with advanced NSCLC and merits a l-2 course therapeutic trial in such patients. The schedule should also be assessed as primary (neoadjuvant) chemotherapy before radical radiotherapy for locally advanced NSCLC in a random&d trial.

ApbueIl#udyofttxombiithterfemn-gammafolbwingcombhth chemotherapy for patients with extensive small cell long cancer Bitran JD, Gmen M, Perry M, Hollis DR, Hcmdon JE II. Division ofHemoto/ogy/

i%coiogy. Lutheran General Hospital. 1600 Dempstm Park Ridge, iL 60068- 1161. Am J Clin Oncol Cancer Clin Trials 1995;18:67-70.

A total of 71 patients with cxtcnsivc small cell lung cancer were enrolled in CALGB study 8733. Chemotherapy was administcrcd with cisplatin 33 mglm’, iv. infusion days 1-3, doxorubicin 45 mp/m’ iv. day 1, cyelophosphamidc 800 mp/m’ i.v. day 1, and ctoposidc 80 ms/m’ iv. infusion days l-3 (PACE). Following four cowsea ofPACE, patients achieving a CR or PR were started on recombinant intcrfcron-gamma (rINF-gamma) 0.2 rng s.c. daily until grade IV toxicities or progression occurred. Of the 71 patients cnrollcd, 67 are evaluated (47 males and 20 fcmelee), mcdien age 59 years, end median PSI. The response rate to PACE was 48/67, 72%. Grade 3-4 toxicities included granulocytopcnia, thrombocytopenia, and tive trcatmsnt-ml&d deaths (7%). Forty-one patients were started on rINF-gamma. Of these 4 1 patients. 11 were in CR, 30 in PR. The objective response rate to rINF-gamma was 2130 or 6.7%. Recombinant rINF- gamma is inactive in small cell lung cancer, cvcn when the tumor burden has been substantially reduced by prior chemotherapy.

C~t~shtiwoCiaterleukib2p~stumoroee~sfPctor in advanced non-small cell long cancer

Schillcr JH, Morgan-Ihrig C, Levitt ML. Comprehensive Concer Center: lJniversi& of Wwmstn, 600 Higltland Avenue. Madison. WJ 53792. Am J Clin Oncol Cancer Clin Trials 1995;18:47-51.

Based upon in vitro and clinical data suggesting antitumor activity of interlcukin-2 (IL-2) plus tumor necrosis factor (TNF) in non-small cell lung crower (NSCLC), WC conducted two parrdlcl pilot stodics of the combination in patients with dvanccd disease. Eight patients at the University of Wisconsin received 6 x 10” intcmational U/r&day of IL-2 by continuous infusion on days l-2, 8-I 1, and 15-18 with 50 iglm’iday of INF administered intramuscularly on the wnc days. Seven patients at the University of Pittsburgh received IL-2 as a continuous infusion for 5 days at a dose of 6 x LO6 U/mf/day, way 14 days. TNF was administcrcd intramuscularly on days 1 through 5, starting at a dose of 50 id m’. Paticnts with no evidence of grade 3 or 4 toxicity on the first cycle had their dose of TNF escalated from 50 to IO0 and then to I50 ig/&. No responses were observed. The therapy was not well tolerated, with I 1 of 15 patients developing grade 3 or 4 toxicity et some point during their therapy. The most common grade 3 or 4 toxicities were pulmonary (6 episodes) or cardiac (4 episodes) events. Constitutional symptoms were common, but not dose-limiting. Despite the lack of observed responses, the median survival was 11 months, with one patient with metestatic discasc alive over 30 months later. WC conclude that IL-2 plus TNF was not cffcctivc in inducing responses in patients with advanced NSCLC, but the prolonged survival suggests a role for IL2 in NSCLC, which weds to bc further defined by means other than classic response criteria.

Qu~ityversusqusatityotlaeiathetrePtmeatdpatieatPwithadvPoeed smallcell long caocer? A randomized phase III comparisoo ofweekly carboplatin and teniposide versus cisplatin, adriamycio, etoposide alternating witb cyclopbospbamide, metbotrexate, vincristioe and lomostine Joss RA, Albert0 LP, Horny C, Bacchi M, Leyvraz S, Thurlimann B et al

Division of Oncolo~ Deporbnent o/Medicine. Kantonsspital, CH-6000 Lurem 16. Ann Oncol 1995;6:41-8.

BockgwunB Baxd on a promising pilot study with weekly carboplatin and teniposidc (CBDCA’VM) the Swiss Group for Clinical Cancer Rcscarch (SAKK) performed a randomixd phase m trial in patients with cxtensivediscase small- cell lung cancer aimed at the development of an effective palliative trcatmcnt with low subjective toxicity. Potimtsmdmethods: From September 1989 to September 1991 patients were randomised to a weekly regimen of CBDCANM or to our ‘standard chemotherapy’ of cisplatin, adrismycin and etoposidc alternating with cyclophosphamide, methotrexate, vincristinc and lomustine (PAVCyMOC). Results: The trial was closed before the planned accrual of 140 cvaluable patients due to a sign&ant survival difference shown by an i&rim analysis. Of the 61 patients 59 were eligible and included in the final analysis. The results achieved with the PAV-CyMOC regimen were significantly bcttcr than those observed in patients treated with weekly CBDCANM (remission rate of 65% vs. 29%; p =