Faculty Collaboration Database

Preclinical and pilot clinical studies of docetaxel chemoradiation for Stage III non-small-cell lung cancer. Int J Radiat Oncol Biol Phys 2011 Aug 01;80(5):1358-64

Date

08/17/2010

Pubmed ID

20708854

Pubmed Central ID

PMC3268047

DOI

10.1016/j.ijrobp.2010.04.060

Scopus ID

2-s2.0-79960100485 (requires institutional sign-in at Scopus site)   6 Citations

Abstract

PURPOSE: Local and distant failure rates remain high despite aggressive chemoradiation (CRT) treatment for Stage III non-small-cell lung cancer. We conducted preclinical studies of docetaxel's cytotoxic and radiosensitizing effects on lung cancer cell lines and designed a pilot study to target distant micrometastasis upfront with one-cycle induction chemotherapy, followed by low-dose radiosensitizing docetaxel CRT.

METHODS AND MATERIALS: A preclinical study was conducted in human lung cancer cell lines NCI 520 and A549. Cells were treated with two concentrations of docetaxel for 3 h and then irradiated immediately or after a 24-h delay. A clonogenic survival assay was conducted and analyzed for cytotoxic effects vs. radiosensitizing effects of docetaxel. A pilot clinical study was designed based on preclinical study findings. Twenty-two patients were enrolled with a median follow-up of 4 years. Induction chemotherapy consisted of 75 mg/m(2) of docetaxel and 75 mg/m(2) of cisplatin on Day 1 and 150 mg/m(2) of recombinant human granulocyte colony-stimulating factor on Days 2 through 10. Concurrent CRT was started 3 to 6 weeks later with twice-weekly docetaxel at 10 to 12 mg/m(2) and daily delayed radiation in 1.8-Gy fractions to 64.5 Gy for gross disease.

RESULTS: The preclinical study showed potent cytotoxic effects of docetaxel and subadditive radiosensitizing effects. Delaying radiation resulted in more cancer cell death. The pilot clinical study resulted in a median survival of 32.6 months for the entire cohort, with 3- and 5-year survival rates of 50% and 19%, respectively, and a distant metastasis-free survival rate of 61% for both 3 and 5 years. A pattern-of-failure analysis showed 75% chest failures and 36% all-distant failures. Therapy was well tolerated with Grade 3 esophagitis observed in 23% of patients.

CONCLUSIONS: One-cycle full-dose docetaxel/cisplatin induction chemotherapy with recombinant human granulocyte colony-stimulating factor followed by pulsed low-dose docetaxel CRT is promising with regard to its antitumor activity, low rates of distant failure, and low toxicity, suggesting that this regimen deserves further investigation.

Author List

Chen Y, Pandya KJ, Hyrien O, Keng PC, Smudzin T, Anderson J, Qazi R, Smith B, Watson TJ, Feins RH, Johnstone DW

Author

David Johnstone MD Professor in the Surgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Antineoplastic Combined Chemotherapy Protocols
Carcinoma, Non-Small-Cell Lung
Cell Line, Tumor
Cisplatin
Combined Modality Therapy
Drug Administration Schedule
Female
Follow-Up Studies
Granulocyte Colony-Stimulating Factor
Humans
Lung Neoplasms
Male
Middle Aged
Pilot Projects
Radiation-Sensitizing Agents
Recombinant Proteins
Remission Induction
Taxoids
Tumor Stem Cell Assay