Abstracts/Lung Cancer I2 (I995) 265-329

Improved control in both areas will be necessary to meaningfully enhance outcome for the universe of Stage III NSCLC patients. Several randomized trials show a significant survival benefit when cisplatin-containing induction chemotherapy is administered prior to locoregional treatment. In the favorable subset of Stage III patients s&&d for study by CALGB, the surviving fraction at 2-5 years post-therapy was 2-fold larger in the chemoradiation group than in the cohort treated with radiation alone. The French trial documented a significant decrease in distant metsstases rate among the chemotherapy treated patients. In all the trials where patterns of failure are discussed, local disease persistence is the overwhelming rule. Future trials must evaluate improved induction chemotherapy approacha. S-e III patients am an ethical population in which to test induction tbapy with new drug combinations random&d against already ‘active’ regimens for comparative efficacy. End points would be initial response rates, patterns of failure, and overall survival. The feasibility of high-dose chemotherapy regimens with growth factor and hcmatopoietic support followed by aggressive radiation must be tested. If feasible, trials randomizing high dose versus cawentionel dose induction programs within the context of sequential multimodality therapy should follow. Intensified radiation approaches such as hypcrfractionation or CHART should be paired with active concurrent chemotherapy following induction chemotherapy alone. Pursuit of these approaches over the next several years will hopefully produce major impmvnncnts in treatment efticaey and lead to enhanced survival mpcctations for the large group of patients worldwide with Stage III NSCLC.

Combined multimodality treatmeat for non-small cell lung caacer - Witb special nzference to pre- and post-operative adjuvaat therapy Watanabe Y. Deporbmnf ojdurgery I, Kanarawa Universify Sch. of Medicine, 13-1 Takara-mochi, Kanazawa 920. Jpn J Cancer Chemother 1994;21:2555-63.

Surgical resection is the treatment of choice for patients with localiied non- small cell lung cancer. However, the long-term survival rate of patients after such surgery is disappointing. Even in stage I patients who have undergone potentially curative operation, over 30% of them recur within five years. Most of the recurrences are caused by hematogenous metastases to the distant organs. However, all of the comparative study to evaluate postoperative adjuvant therapy, ie, chemotherapy, immunotherapy, radiotherapy, or their combination, showed negative results, except for a few positive outcomes. To date, there is no evidence that pn- and postoperative adjuvant therapy have shown a favorable impact on survival of postoperative patients with stage I disease. LCSG has had reportedly favorable results on survival of stage II and III adenocarcinoma and large cell carcinoma by postoperative CAP-chemotherapy. Postoperative chemotherapy and/or radiotherapy showed no impact on survival of stage III patients who underwent surgical intervention. However, preoperative induction therapy (IT) psing combination chemotherapy (with or without radiotherapy) has improved be survival of patients with resected stage III disease, although most reports are of phase II trial or interim results. It seems to be true that the IT can render an advanced lung cancer w&able and also can control prwxisting micro-metastases in the distant organs. However, randomized prospective trials are required for evaluating an impact on the survival rate of the advanced non-small cell lung mm.

Current status of aeoadjwaot therapy for non-small cell lung cancer Falser LP. Rush-Presbyterian-SLMC, Chicago, IL. Chest:1994;106:Suppl:355S- 8S.

Any program of therapy for clinically advanced non-small cell lung cancer (NSCLC) that would increase the incidence of local tumor control and decrease the likelihood of distant mettiatic disease would be of obvious benefit. The objective of neoadjuvant therapy is to eradicate the primary tumor and micrometastatic disease. In the past IO years, many trials have been completed to evaluate neoadjuvant therapy and they have included sequential chcmoradiotherapy, concurrent chemoradiothcrapy. chcmotherapyfsurgcq, and chemoradiation/surgcry. These trials have predominately ban phase 2 trials and have demonstrated that chemotherapy is generally well tolerated, surgery is technically feasible, and operative morbidity and mortality are not excessive. Long-term survival for patients with clinically advanced NSCLC is improved when compared with historic controls. These trials have demonstrated B greater then 50% clinical response rate and in approximately 20% of patients who have undergone resections, the tumor is steri&-d. This latter group of patients demonstrate significantly improved survival. Cost-benefit ratios and quality of life have yet to be evaluated Final de&nation ofthe effectiveness ofneoadjuvant therapy for NSCLC awaits completion of phase 3 trials.

Raodomized phase 2 evaluatioo of preoperative radiation therapy aad preqerative cbemotberapy with mitomycia,viablastiae, aad cisplatia ia patientswith tecbaically unresectablc stage IIfA aad IlIE non-small cell cancer of the long: LCSG 881 Wagner H Jr, Lad T, Piantadosi S, Ruckdeschcl JC. H. LueMofi~f Cancer Cenfer. 12902 Magnolia Driw. Tampa. i?L 33612. Chest l994;106:Suppl:3448S-54S.

Behveen June 1988 and January 1980.67 patients with pathologic stage IU non-small cell lung cancer were randomized to receive either preoperative mitomycin, vinblastine, and cisplatin (MVP) chemotherapy (cisplatin 120 mpi m’, and mitomycin, 8 mp/m’ day 1+29, and vinblastinc, 4.5 mg/m’ on day 1, IS, 22, and 29 and 2.0 mg/m’ day 8), or preoperative radiotherapy (44 Gy in 22 fractions to the primary tumor and media&urn). The purpose of this study was to identify a treatment approach that showed suffzient effectiveness and acceptable toxicity to warrant testing by prospective randomized trial against ‘standard’ nonsurgical treatment. All patients had surgical staging of the mediastinum and had either unresectable N2 disease or T4 disease with proximal extension of disease along the pulmonary artety. Response to preoperative therapy WBS evaluated 8 WC& atIer beginning treatment and patients with complete or partial radiographic response were to undergo surgical exploration and resection if possible. Fitly-seven patients were eligible and evaluable for response. Of the 67 total patients, 3 were unavailable for follow-up, 4 were ineligible, I was canceled, and 2 refused all treatment aRer having been randomized. Ofthe eligible and evaluable patients, 49 had stage IIIA and 8 had stage IIIB disease. Randomization was to MVP in 26 cases and to radiotherapy (XRT) in 3 I. Radiographic response to treatment was virtually identical for the hva approaches, with 29 of the 57 cvaluable patients achieving objective responses. In patients achieving radiographic response, 24 underwent surgical exploration and 20 underwent resection, of which 18 were complete. The mediastinum WBS free of tumor in seven patients but only two pathologic complete responses were seen (one each to XRT and MVF’). In addition, ten nonresponders undetwent surgery; seven underwent resection. Median survival for the entire group is I2 months, with a 27% actuarial survival at 4 years. Two patients died of treatment toxicity during preoperative therapy. Overall toxicity included 2 preoperative toxic deaths and 6 postoperative deaths in 34 patients who underwent surgical exploration (3 each with XRT and MW) due to adult respiratory distress syndrome (3), myocardial infarction (I), pulmonary edema (I), and esophageal tistula (I), for an overall death rate 8 of 57 (14%) and a perioperative death rate in surgically explored patients of 6/34 (I 8%). These preoperative regimens, in the population studied her&, were of modest effxacy and substantial toxicity while these data do not exclude possible gain in long- tern survival for these preoperative treatments compared with the best nonsurgical therapy, until such benefits are documented in prospective trials, their use should be considered investigational.

Preoperativechemotherapy (cisplatia aad fluorwracil) aad radiation tberapy ia stage III mm-small cell lung caacer. A pbase 2 study of the USG Weidcn PL, Piantadosi S. wrginia Muson Medico/ Cir Sea~le, Bclfliinore. MD. Chest 1994,106:Suppl:344S=IS.

Shrdy objective: To determine the feasibility, toxicity, and potential efkacy of neoadjuvant chcmoradiotherapy before surgery in patients with non-small cell lung cancer limited to tbc chest. Design: Phase 2 pilot shrdy. Selling Multi- institutional, multimodality cooperative group. Patients: Eight-five patients with advanced stage III-A or minimal stage III-B non- small cell lung cancer in whom attempted resection would have been likely to leave residual disease. Intervention: Cisplatin, 75 mg/m’, was given on days 1 and 29; fluorouracil, I g/m’ for 24 h, was given as B continuous infusion on days I to 4 and 29 to 32; thoracic radiation, 30 Gy in I5 fractions, was administered on days 1 to 19. Thoracotomy with twnor resection wes planned for day 57. MeosuremenLr ond mwfm Two patients achieved a complete and 46 achieved a partial response afier the neoadjuvant chcmoradiotherapy for an overall response rate of 56%. Toxicity was moderate but acceptable. Fifty- four patients underwent tboracotomy and tumor resection was attempted in 44; 29 (34%) had complete and 15 (18%) had incomplete resections. There was no apparent increase in postoperative complications. In eight patients (9%). no viable tumor was detected pathologically in the resection specimen. Of the 18 patients whose tllmors were completely resected and had disease recurrence, none had recurrence only in the chest, I5 (83%) had re~“mm~e in distal sites, and 3 (17%) developed second primaly tumors. Median survival of all patients was I3 months. Concfusions: This neoadjuvant regimen did not appear to provide maJor benefit in patients with advanced but potentially resectable non-small cell lung cancer. Further studies are needed to better define the relative roles of preoperative radiotherapy and chemotherapy.