Phase II study of low-dose paclitaxel with timed thoracic radiotherapy followed by adjuvant gemcitabine and carboplatin in unresectable stage III non-small cell lung cancer.
OBJECTIVE
The purpose of the proposed study is to evaluate the effectiveness and safety of low-dose paclitaxel with timed thoracic radiotherapy (TTR) for local control by inducing maximum radiosensitization through G2-M phase cell cycle arrest, followed by full dose adjuvant chemotherapy with gemcitabine and carboplatin for eradication of possible micrometastasis in unresectable stage III non-small cell lung cancer (NSCLC).


METHODS
This is a single-center, non-randomized prospective phase II study. Patients with unresectable stage III NSCLC were treated with paclitaxel 15 mg/m(2) IV, followed by TTR 6 h later on Monday/Wednesday/Friday, and TTR only on Tuesday/Thursday mornings (total 55 Gy). Full dose adjuvant chemotherapy consisted of intravenous carboplatin (AUC 5) on day 1, gemcitabine 1000 mg/m(2) on days 1 and 8, every 21 days for 4 cycles. The primary endpoint was overall survival (OS). Secondary endpoints were overall response rate (ORR), and toxicities.


RESULTS
Twenty-seven patients were eligible for the study. Patient characteristics were: 19 males (70%); median age 67 years (range 39-82); 15 (56%) stage IIIB; 89% with ECOG performance status ≥1. Three-year OS was 16.7% in all patients, and 27.3% in patients received three or more cycles of adjuvant chemotherapy, respectively. ORR was 63%. Grade 3 toxicities during paclitaxel plus concurrent TTR phase were radiation esophagitis (11%) and radiation pneumonitis (4%), no grade 4 toxicities occurred. One grade 5 hemoptysis. Grade 3/4 toxicities during adjuvant gemcitabine/carboplatin were pneumonitis (22%), anemia (30%), neutropenia (22%), and thrombocytopenia (33%), one grade 5 neutropenic fever.


CONCLUSIONS
Low-dose paclitaxel with concurrent TTR is an effective chemoradiotherapy regimen in unresectable stage III NSCLC. Improved survival benefit was observed in patients who have received three or more cycles of full dose adjuvant chemotherapy, yet, gemcitabine related radiation pneumonitis and hematological toxicities limited adjuvant chemotherapy delivery.
Leo Jenkins Cancer Center, Division of Hematology Oncology, Department of Internal Medicine, Brody School of Medicine, East Carolina University, Greenville, NC, United States; Department of Medicine, Section of Hematology Oncology, Baylor College of Medicine, Houston, TX, United States.
Jun
J
Zhang
Department of Radiation Oncology, Washington University, School of Medicine, Saint Louis, MO, United States.
Hiram A
HA
Gay
Department of Radiation Oncology, Mitchell Cancer Institute, University of South Alabama, United States.
Suzanne
S
Russo
Leo Jenkins Cancer Center, Division of Hematology Oncology, Department of Internal Medicine, Brody School of Medicine, East Carolina University, Greenville, NC, United States.
Teresa
T
Parent
Leo Jenkins Cancer Center, Division of Hematology Oncology, Department of Internal Medicine, Brody School of Medicine, East Carolina University, Greenville, NC, United States.
Raid
R
Aljumaily
Leo Jenkins Cancer Center, Division of Hematology Oncology, Department of Internal Medicine, Brody School of Medicine, East Carolina University, Greenville, NC, United States. Electronic address: walkerp@ecu.edu.
Paul R
PR
Walker
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000628:therapy*; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D011878:Radiotherapy; D013909:Thorax / Q000473:pathology / Q000528:radiation effects*; D000093542:Gemcitabine
D003841:Deoxycytidine; D016190:Carboplatin; D017239:Paclitaxel; D000093542:Gemcitabine
Chemoradiotherapy; Gemcitibine/carboplatin; Non-small cell lung cancer; Timed thoracic radiation; Unresectable