RTOG 0017: a phase I trial of concurrent gemcitabine/carboplatin or gemcitabine/paclitaxel and radiation therapy ("ping-pong trial") followed by adjuvant chemotherapy for patients with favorable prognosis inoperable stage IIIA/B non-small cell lung cancer.
OBJECTIVE
The optimal dose of gemcitabine that can be used with concurrent radiation therapy for locally advanced non-small cell lung cancer has not been well defined. This trial addresses this question in an alternating sequence "ping-pong" design trial to find the maximum tolerated dose (MTD) for gemcitabine/carboplatin (Sequence A) or gemcitabine/paclitaxel (Sequence B) and thoracic radiation therapy followed by adjuvant gemcitabine/carboplatin chemotherapy.


METHODS
Thirty-five patients with histologically confirmed Stage IIIA/B non-small cell lung cancer were entered into two separate sequences, each with multiple cohorts. A dose level was considered acceptable if, of the first six eligible patients on each cohort, fewer than three experienced dose limiting toxicities.


RESULTS
Sequence B of this 2 sequence "ping-pong" trial closed early due to toxicity in cohort 2 (gemcitabine 300 mg/m/wk and paclitaxel 30 mg/m/wk). On Sequence A, the MTD was the cohort 5 dose: gemcitabine 450 mg/m/wk and carboplatin 2 area under curve (AUC) concurrently with thoracic radiation. Cohort 7 (gemcitabine 600 mg/m/wk and carboplatin 2 AUC) showed 4 dose limiting toxicities: 2 grade 3 esophagitis; one grade 3 febrile neutropenia; and one grade 4 neutropenia.


CONCLUSIONS
Concurrent gemcitabine/paclitaxel chemoradiation regimen followed by adjuvant gemcitabine/carboplatin produced excessive toxicity at the lowest tested dose combination and was not suitable for further study in this trial. Meanwhile, the MTD of concurrent gemcitabine/carboplatin chemoradiation was determined to be gemcitabine 450 mg/m and carboplatin AUC-2. This combination was found to be tolerable. Although not a primary end point, survival results are summarized as well.
Choy
Hak
H
UT Southwestern Medical Center, Dallas, Texas, USA. hak.choy@utsouthwestern.edu
Jain
Anshu K
AK
Moughan
Jennifer
J
Curran
Walter
W
Whipple
Gary
G
Demas
William F
WF
Ettinger
David S
DS
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D019540:Area Under Curve; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000532:radiotherapy* / Q000556:secondary; D015331:Cohort Studies; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage; D011379:Prognosis; D011879:Radiotherapy Dosage; D012074:Remission Induction; D015996:Survival Rate; D016896:Treatment Outcome; D000093542:Gemcitabine
D003841:Deoxycytidine; D016190:Carboplatin; D017239:Paclitaxel; D000093542:Gemcitabine