Abstracts/Lung Cancer 12 (1995) 265-329

per day. While severe esophagitis was reduced, grade 4 thrombocytopenia tanme mom prevalent and was seen in 6 of 7 patients. In-field hlmor responses were observed in 17 of 28 evaluated patients with non-smallcell lung cancer. The median times to progression end survival were 4 and 6 months, respectively. When only patients with all known disease confined to the radiotherapy ticld were considered the comspondin8 times were 6 and 15 months, rcspcctively. Most treatment failures occurred outside of the irradiated field. Conclusions: (1) This intensive multimodality regimen can be given with aggressive supportive care incorporating GCSE The recommended phase II doses for a 4-week cycle are cisplatin 50 mdm’ week 1, and 100 mpirnl week 2, IFN 2.5 MU, HU 500 mg every 12 h x I1 and S-FU 800 mp/m’ per day with single fraction radiotherapy during weeks l-3 and GCSF:during weeks 1,3, and 4. (2) GCSF can be safely administered and provides effective support of neutmphils when administered simultaneously with IFN, cisplatin, and chest radiotherapy. (3) There is synergistic renal toxicity when high doses of IFN and cisplatin are given together. (4) Hypxfractionatcd radiotherapy decreases the severity of esophagitis but incresses thrombocytapenia. (5) Although highly toxic, nxponse rate?., time to progression and survival figures with this regimen are encouraging and support its investigation in the phase II setting.

Combined-modality treatment ofsmall-cell lung caocerz Randomized cmnparisuoofthrecioductioocbemotherapiesfdbwedbymaioteoaoce cbemotherapywitborwitbad radiotberapytotbechest Joss RA, Alberta P, Bleher EA. Ludwig C, Siegenthaler P, Martinclli G et rd. Division of Oncology. Deparbnmi ofMedicine. Kantonsspilal, CH-6000 Lruem 16. Ann 0no.d 1994;5:921-8.

Background: From 198Oto 1983 thcSwissGmupforClinicalCancer Research (SAKK) performed a randornised phase III trial in patients with smallccll lung cancer with the objective of impmving the results of induction chemotherapy and defining the role of consolidating chest irradiation. Palienls and methods: Patients were initially randomized to induction arms AVP (adriarnycin, etoposide and cisplatin given every four weeks for four cycles), EVA (cyclophosphamide, ctoposidc end adriamycin given every four weeks for four cycles) or MOCIAVP (mcthotrexatc. vincristine, cyclophosphamidc alternating with adriamycin, ctoposidc and cisplatin given for hvo cycles). All patients received prophylactic cranial irradiation with 30 Gy, and aAcr four months of induction chemotherapy were randomized to maintenance chemotherapy with or without consolidating chest irradiation. The patients in the combined-modality maintenance arm first received radiation therapy to the chest (45 Gy) followed by MOC/EVA chemotherapy. Resuk 266 patients were eligible and cvaluable. An overall response rate of 70% with 21% of complete remissions, a median survipossiblc, depending on the appearance of the coating).

Phase I trial of outpatient weekly paclitaxel sod concurrent radiation tberapy for advaoced non-smalkell lung caocer Choy H, Akerley W, Safran H. Clark J, Rege V, Papa A et al. Deporbrrenr of Radiation Therapy Rhode Island Hospiral. 593 Ed+ St, Protidence, RI 02903. J Clin Oncol 1994;12:2682-6

Purpose: To determine the maximum-t&rated dose (MTD) and dose-limiting toxicities of paclitaxel administered weekly on an outpatient basis with concurrent thoracic radiation to patients with advanced non-small-cell lung cancer @ISCLC). Pafients andMefhods: In this phase I clinical trial, paclitaxel was administered as a 3-hour intravenous (Iv) infusion, repeated every week for 6 weeks. The starting dose of paclitaxcl was 10 mg/m? Doses were escalated at IO-mgim’ increments in successive cohorts of three new patients if tolerated Unacceptable toxicity was defined IIS grade 3 nonhcmatologic toxicity, excluding nausea and vomiting, and grade 4 hcmatologic toxicity according to Cancer and Leukemia Group B expanded ccvnrn~n toxicity criteria. Radiation was administered to the primary tumor and regional lymph nodes (40 Gy) followed by a boost to the tumor (20 Gy). Resrrfrr: Twenty-seven patients were entered onto this study through seven dose escalations (from 10 mgim?lwk to 70 mglm’iwk for 6 weeks). Severe csophagitis occurred at 70 mp/m’ (two patients with grade 4 disease end one patient with grade 2). One of six patients at 60 mglm’ developed grade 3 csophagitis and three of xven patients had grade 2 csophagitis. One of 27 patients developed a hypersensitivity reaction. One of 27 patients developed grade 3 neutropenia. Conclusion: Esophagitis is the principle doselimiting toxicity of weekly paclitaxel and thoracic radiation in the outpatient setting. A phase II trial using concurrent radiation and paclitaxcl at the MTD of 60 mg/m’/wk is underway.

Cambl cbemotberapy sod radiotherapy: From biology tolwd-kde Hennequin C, Favaudon V, Balosso J, Marty M, Maylin C. Service Cancerologie- Radiotherapie. Hopiral Saint-Louis, 1. Avenue Claude-Villefiur~ 75010 Paris. Bull Cancer 1994;81:1005-13.

Combination of radiotherapy and chemotherapy (CRC) is actually one important way of research in oncology. Theoretical advantages are: 1) Spatial cooperation; 2) Additivity, which is only obtained if the toxicity of each modality arc different; 3) Supra-additivity, which needs a rigourous in vitro definition; the only way to prove it is to make an isobologram analysis. This model has however, some limitations: qualitative variable could not be used, results could be different, depending on the cell line and isoeffect chosen... In fact, a supra- sdditivity was only demonstrated for cisplatinum and etoposidc. Interactions mechanisms were: 1) at the molecular level, creation of new lesions or inhibition of radiation lesions repair, 2) At the cellular level, either cytokinetic cooperation with S-phase dcpcndant drugs, or synchronisation for the drugs which blocked the cells in M-phase; 3) At the tissular level, roxygenation, cycle redistribution... In clinical practicc,thra main schedules have ban described: sequential, alternating and concomitant. Only the latter try to use the supra-additivity phenomena. Aims ofCRC could bc: improvement or in survival or in local control, preservation of e functional organ... Dcpcnding on the tumor site and aim of the CRC, sane schedules had to be preferred. For head and neck cancers, alternating or concomitant schedules offer a better local control. In bronchial carcinomas, sequential administration of the hvo modalities reduce the m&static rate, but not the local control. Concomitant schedule improve the local control rate only. In some conservative protocol of bladder cancers, sequential and concomitant administration were used. In conclusion, CRC begins to be the usual clinical practice. The present schedules could be improved with the help of laboratory findings, which are now more and mare precise.

--npY(~~rdatberrpY@~~loepuy- wo-small cell bmgcaneer (NSCLC): A review Mirimanoff RO. Deparbnent ofRadiation Oncolo~, Centre Hosp. Universilaiie Vaudois, CHW 1011 Lousannc. Lung Cancer (Ireland) 1994;l I:Suppl 3:S79- S99.

Stage III or locally advanced non-mctastatic, non-small cell lung cancers comprise about 40% of all NSCLC. A proportion of patients with Stage III NSCLC can be trented by induction RT/CT followed by surgery, but the majority, in particular all Stage IIIB, are not candidates for this approach. For these patients, RT alone is generally considered LLS the standard treatment. RT has a modest, but definitive curative potential, with l-, 2-, and S-year survivals of about 40%, 20% and 5%, respectively, and median survival of 9-12 months. Combination CT-RT, depending on its type and rationale, is aimed at improving survival via a decrease oflocal or distant failure r&sorb& Combined modality (CM)can be subdivided into 3 categories: sequential, concomitant and alternated regimes. Concomitant and alternated CT-RT have some common characteristics and rationale, the overall time playing a central role. This paper reviews studies of inoperable NSCLC treated with these CM, excluding sequential CT-RT trials, which would require a separate discussion. Numerous Phase I-II shrdics have been recently published on concomitant or alternated schemes and 33 of them are presented in this paper. Although it is hazardous to readily compare their results with those of RT-alone studies, several trials using platin-based combination chemotherapy, concurrently or alternated with RT, have show impressive response rates and encouraging survivals, at B price of significant toxicity. Seven randomized trials comparing RT alone vusus concomitant CT-RT are now available: the 3 noncisplatin trials have failed to show any improvement in survival with CM, whereas among the 4 cisplatin trials, only one demonstrated a benefit with lowdose cisplatin added to RT. Implications for future clinical research will be discussed.

Tbe role of induction cbemotberapy before radiation therapy in non- operativeman~gemeatofstagelIINSCLC Green h4R. Uniwzrsi@ of Colrj&rria. Medical Cenrer: 200 West Arbor Drive 8421, San Diego, CA 92103-8421. Lung Cancer (Ireland) 1994;I I:Suppl3:S55- S65.

Radiation therapy alone has been ‘standard’ management of patients with Stage IIl non-small cell lung cancer for several decades. Palliative benefits arc routinely achieved but significant survival bcnetits have not been documented Patterns of failure in Stage III patients emphasize the need to pursue better treatment for both local macroscopic disease and distant micromctastatic sites.