title: Carboplatin, etoposide, and radiotherapy, followed by surgery, for the treatment of marginally resectable non-small cell lung cancer.
abstract: The present study was undertaken in order to determine the feasibility and efficacy of induction chemotherapy with carboplatin and etoposide, followed by weekly carboplatin and full-course radiotherapy as pre-operative therapy for marginally resectable non-small cell lung cancer (NSCLC). Twenty-eight patients with good Eastern Cooperative Oncology Group (ECOG) performance status ratings and stage IIIA NSCLC received induction chemotherapy with carboplatin (dose computed with the Egorin formula, days 1 and 29) and etoposide (100 mg/m2/day, days 1 through 3 and 29 through 31). This was followed by 100 mg/m2 weekly carboplatin given over 6 weeks, concurrently with 60 Gy radiotherapy. Patients with either responsive or stable disease underwent thoracotomy 4 weeks after the completion of combined-modality therapy. All 28 patients received the first chemotherapy cycle (average carboplatin dose, 407 mg/m2; range, 195 to 586 mg/m2). World Health Organization (WHO) grade 3/4 neutropenia and thrombocytopenia were observed in 53 and 34% of patients, respectively. There were three febrile neutropenic episodes, but no septic deaths. Five patients (18%) required dose reductions prior to the second chemotherapy cycle, but the dose intensity of carboplatin was maintained (average dose, 390 mg/m2; range, 195 to 586 mg/m2). In all, 82% of patients received full-dose radiotherapy, and 73% received at least five of six planned concurrent weekly carboplatin doses. Carboplatin doses were most frequently delayed for thrombocytopenia and/or leukopenia. Carboplatin did not increase the incidence of radiation-induced esophagitis. Only three patients required interruption of radiotherapy, for esophagitis (two patients) and persistent thrombocytopenia (one patient). The response rate to pre-operative therapy was 64%. In this study, we demonstrated the ability to deliver escalated doses of carboplatin with standard-dose etoposide as induction chemotherapy with reasonable myelotoxicity. The combined-modality therapy was well tolerated, and the addition of weekly carboplatin did not result in increased radiation-related toxicity. This neoadjuvant regimen is active in the treatment of locally advanced NSCLC, and compares favorably to other cisplatin-based regimens.
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710.
authors.forename: M A
authors.initials: MA
authors.lastname: Deutsch
authors.forename: K A
authors.initials: KA
authors.lastname: Leopold
authors.forename: J
authors.initials: J
authors.lastname: Crawford
authors.forename: W
authors.initials: W
authors.lastname: Wolfe
authors.forename: W
authors.initials: W
authors.lastname: Foster
authors.forename: S
authors.initials: S
authors.lastname: Blackwell
authors.forename: R
authors.initials: R
authors.lastname: Yost
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage*; D002289:Carcinoma, Non-Small-Cell Lung / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D005047:Etoposide / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D013908:Thoracotomy
chemical_list: D005047:Etoposide; D016190:Carboplatin