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Chemotherapy in Combined Modality Regimens

Updated February 2008 


Chemotherapy should be a platinum-based regimen.

Sequential Chemoradiation

Sequential therapy is a consideration in individuals otherwise fit enough to receive combined modality therapy, but decline concurrent chemoradiation for personal reasons. As this method is not favored, there is limited data on chemotherapy combinations, published regimens include cisplatin-vindesine-cyclophosphamide-lomustine, cisplatin-vinblastine and cisplatin-vinblastine followed by thoracic irradiation.1-3 At the BCCA, cisplatin-based therapy is the chemotherapy option of choice.

Concurrent Chemoradiation

Concurrent cisplatin-etoposide chemotherapy plus thoracic irradiation has been widely used in NSCLC. Carboplatin may be substituted in situations where patients are unable to tolerate cisplatin due to co-morbid disease or toxicity. The platinum-etoposide combination can be delivered at full systemic doses with radiotherapy, rendering it the preferred drug regimen.

Third generation cytotoxics have been explored in combination with radiotherapy. Many are associated with increased normal tissue toxicity and as a result the doses with radiotherapy need to be attenuated eg. gemcitabine, docetaxel, vinorelbine and paclitaxel.4,5 This therapeutic strategy focuses on the radiosensitizing effect of the drugs, however, may undermine the efficacy of therapy from a systemic perspective.

Consolidation Chemotherapy

Consolidation chemotherapy has been explored in an effort to improve systemic control of disease by adding a non-cross reactive agent post-chemoradiotherapy with a platinum based regimen. The most commonly evaluated drug has been docetaxel.6,7 In two phase II studies there appeared to be a benefit to the addition of consolidation docetaxel. However, a larger phase III trial conducted by the Hoosier Oncology Group (HOG) failed to confirm this result.8 Current recommendation at the BCCA is for two cycles of platinum-etoposide chemotherapy concurrent with radiotherapy followed by two cycles of consolidation platinum-etoposide alone. The need for 4 cycles of treatment has been brought into question by the HOG study. However, until further data becomes available, adequate delivery of platinum in the upfront setting is felt to be most important.

References:​

1. Dillman RO, Herndon J, Seagren SL, et al: Improved survival in stage III non-small-cell lung cancer: seven-year follow-up of cancer and leukemia group B (CALGB) 8433 trial.[see comment]. Journal of the National Cancer Institute. 88:1210-5, 1996

2. Le Chevalier T, Arriagada R, Quoix E, et al: Radiotherapy alone versus combined chemotherapy and radiotherapy in unresectable non-small cell lung carcinoma. Lung Cancer 10 Suppl 1:S239-44, 1994

3. Sause W, Kolesar P, Taylor SI, et al: Final results of phase III trial in regionally advanced unresectable non-small cell lung cancer: Radiation Therapy Oncology Group, Eastern Cooperative Oncology Group, and Southwest Oncology Group. Chest. 117:358-64, 2000

4. Maas KW, El Sharouni SY, Smit EF, et al: Sequencing chemotherapy, radiotherapy and surgery in combined modality treatment of stage III nonsmall cell lung cancer. Curr Opin Pulm Med 13:297-304, 2007

5. Rigas JR, Kelly K: Current treatment paradigms for locally advanced non-small cell lung cancer. J Thorac Oncol 2 Suppl 2:S77-85, 2007

6. Gandara DR, Chansky K, Albain KS, et al: Consolidation Docetaxel After Concurrent Chemoradiotherapy in Stage IIIB Non-Small-Cell Lung Cancer: Phase II Southwest Oncology Group Study S9504. J Clin Oncol 21:2004-2010, 2003

7. Sekine I, Nokihara H, Sumi M, et al: Docetaxel consolidation therapy following cisplatin, vinorelbine, and concurrent thoracic radiotherapy in patients with unresectable stage III non-small cell lung cancer. J Thorac Oncol 1:810-5, 2006

8. Hanna NH, Neubauer M, Ansari R, et al: Phase III trial of cisplatin (P) plus etoposide (E) plus concurrent chest radiation (XRT) with or without consolidation docetaxel (D) in patients (pts) with inoperable stage III non-small cell lung cancer (NSCLC): HOG LUN 01-24/USO-023. ASCO Meeting Abstracts 25:7512-, 2007

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