Carboplatin/paclitaxel or carboplatin/vinorelbine followed by accelerated hyperfractionated conformal radiation therapy: report of a prospective phase I dose escalation trial from the Carolina Conformal Therapy Consortium.

Abstract

PURPOSE:

To prospectively determine the maximum-tolerated dose of accelerated hyperfractionated conformal radiotherapy (RT; 1.6 Gy bid) for unresectable locally advanced lung cancer (IIB to IIIA/B) following induction carboplatin/paclitaxel (C/T) or carboplatin/vinorelbine (C/N).

METHODS:

Induction chemotherapy, C/T or C/N, was followed by escalating doses of conformally-planned RT (73.6 to 86.4 Gy in 6.4-Gy increments). Concurrent boost methods delivered 1.6 and 1.25 Gy bid to the gross and clinical target volumes, respectively.

RESULTS:

Between November 1997 and February 2002, 44 patients were enrolled (median age, 59 years; 59% male; stage III, 98%; median tumor size, 4 cm). Thirty-nine patients completed induction chemotherapy: 19 had a partial response, seven progressed, 15 had no response, and three were not assessable. Chemotherapy-associated toxicities were similar in the two chemotherapy groups. The incidence of grade > or = 3 RT-induced toxicity was 1/13, 2/14, and 4/12 at 73.6, 80, and 86.4 Gy, respectively, thus defining the maximum tolerated dose at approximately 80 Gy. Toxicities were in both lung and esophagus and were similar in the two chemotherapy arms. With a median followup of 34 months in the survivors, the actuarial 2-year survival was 47%, the median survival was 18 months. Fifteen patients had tumor relapse: 5 local failures in the high-dose volume, 2 regional failures outside of the high-dose volume, and 8 distant metastases.

CONCLUSION:

High-dose conformal twice-daily radiation therapy to approximately 80 Gy appears tolerable in well-selected patients with unresectable lung cancer following either C/T or C/N. Dose-limiting toxicities are mainly pulmonary and esophageal.

• Authors: Lawrence B Marks, Jennifer Garst, Mark A Socinski, Gregory Sibley, A William Blackstock, James E Herndon, Sunmin Zhou, Timothy Shafman, Andrea Tisch, Robert Clough, Xiaoli Yu, Andrew Turrisi, Mitchell Anscher, Jeffrey Crawford, Julian Rosenman, Carolina Conformal Therapy Consortium
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 22 Issue 21 Pg. 4329-40 (Nov 01 2004) ISSN: 0732-183X [Print] United States
• PMID: 15514374 (Publication Type: Clinical Trial, Clinical Trial, Phase I, Journal Article)

Chemical References

• Vinblastine
• Carboplatin
• Paclitaxel
• Vinorelbine

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Carboplatin (administration & dosage, adverse effects)
• Carcinoma, Non-Small-Cell Lung (drug therapy, radiotherapy)
• Combined Modality Therapy
• Dose Fractionation, Radiation
• Esophagus (pathology, radiation effects)
• Female
• Humans
• Lung Neoplasms (drug therapy, radiotherapy)
• Male
• Middle Aged
• Paclitaxel (administration & dosage, adverse effects)
• Proportional Hazards Models
• Radiotherapy, Conformal
• Survival Analysis
• Treatment Outcome
• Vinblastine (administration & dosage, adverse effects, analogs & derivatives)
• Vinorelbine