A phase I/II radiation dose escalation study with concurrent chemotherapy for patients with inoperable stages I to III non-small-cell lung cancer: phase I results of RTOG 0117.
OBJECTIVE
In preparation for a Phase III comparison of high-dose versus standard-dose radiation therapy, this Phase I/II study was initiated to establish the maximum tolerated dose of radiation therapy in the setting of concurrent chemotherapy, using three-dimensional conformal radiation therapy for non-small-cell lung cancer.


METHODS
Eligibility included patients with histologically proven, unresectable Stages I to III non-small-cell lung cancer. Concurrent chemotherapy consisted of paclitaxel, 50 mg/m(2), and carboplatin, AUC of 2, given weekly. The radiation dose was to be sequentially intensified by increasing the daily fraction size, starting from 75.25 Gy/35 fractions.


RESULTS
The Phase I portion of this study accrued 17 patients from 10 institutions and was closed in January 2004. After the initial 8 patients were accrued to cohort 1, the trial closed temporarily on September 26, 2002, due to reported toxicity. Two acute treatment-related dose-limiting toxicities (DLTs) were reported at the time: a case of grade 5 and grade 3 radiation pneumonitis. The protocol, therefore, was revised to de-escalate the radiation therapy dose (74 Gy/37 fractions). Patients in cohort 1 continued to develop toxicity, with 6/8 (75%) patients eventually developing grade >or=3 events. Cohort 2 accrued 9 patients. There was one DLT, a grade 3 esophagitis, in cohort 2 in the first 5 patients (1/5 patients) and no DLTs for the next 2 patients (0/2 patients).


CONCLUSIONS
The maximum tolerated dose was determined to be 74 Gy/37 fractions (2.0 Gy per fraction) using three-dimensional conformal radiation therapy with concurrent paclitaxel and carboplatin therapy. This dose level in the Phase II portion has been well tolerated, with low rates of acute and late lung toxicities.
Bradley
Jeffrey D
JD
Washington University School of Medicine, St. Louis, Missouri, USA. jbradley@wustl.edu
Moughan
Jennifer
J
Graham
Mary V
MV
Byhardt
Roger
R
Govindan
Ramaswamy
R
Fowler
Jack
J
Purdy
James A
JA
Michalski
Jeff M
JM
Gore
Elizabeth
E
Choy
Hak
H
D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D019540:Area Under Curve; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D002985:Clinical Protocols; D003131:Combined Modality Therapy / Q000379:methods; D019583:Dose Fractionation, Radiation; D004941:Esophagitis / Q000473:pathology; D005260:Female; 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; D017564:Radiation Pneumonitis / Q000473:pathology; D020266:Radiotherapy, Conformal / Q000009:adverse effects / Q000379:methods
D016190:Carboplatin; D017239:Paclitaxel
J Clin Oncol. 2008 May 20;26(15):2457-63
18487565
Int J Radiat Oncol Biol Phys. 1995 Mar 30;31(5):1341-6
7713792
J Clin Oncol. 1999 Sep;17(9):2692-9
10561343
Cancer. 1980 Jun 1;45(11):2744-53
6991092
Lung Cancer. 2004 Oct;46(1):87-98
15364136
J Thorac Oncol. 2007 Jul;2(7 Suppl 3):S94-100
17603311
Int J Radiat Oncol Biol Phys. 2005 Feb 1;61(2):318-28
15667949
Int J Radiat Oncol Biol Phys. 2006 Jul 15;65(4):1106-11
16730134