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Gefitinib for Patients with Stage III NSCLC: A Phase I Study
I. J. Radiation Oncology d Biology d Physics
S476
Volume 69, Number 3, Supplement, 2007
Author Disclosure: L. Geng, None; A. Fu, None; D.E. Hallahan, NIH/NCI, R01-CA1256757, R21-CA128456, R01-CA112385, 2R01-CA89674, R01-CA88076, P50-CA90949, B. Research Grant.
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WITHDRAWN
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Gefitinib (ZD-1839) With Concurrent Docetaxel and Conformal Three-Dimensional Thoracic Radiation Followed by Consolidative Docetaxel/Gefitinib for Patients with Stage III NSCLC: A Phase I Study
A. W. Blackstock, C. A. Jensen, W. J. Petty, T. Oaks, M. Porosnicu, H. Clark, J. F. Lovato, A. Miller Wake Forest University, Winston-Salem, NC Purpose/Objective(s): The safety of 3-dimensional (3D) conformal thoracic radiation delivered with concurrent Gefitinib/Docetaxel chemotherapy in patients with inoperable stage III non-small cell lung cancer (NSCLC) has not been evaluated. In this phase I study we plan to determine the maximum tolerated dose (MTD) of weekly Docetaxel that can be safely delivered with concurrent Gefitinib and a definitive course of 3D conformal thoracic radiation. Materials/Methods: Patients with inoperable stage III NSCLC received weekly intravenous (i.v.) Docetaxel starting at a dose of 15 mg/m2 escalating to 30 mg/m2 in 5 mg/m2 increments and daily Gefitinib (250 mg given orally). Patients received concurrent thoracic radiation to a dose of 70 Gy utilizing 3D techniques. The chemoradiation therapy was followed by 2 cycles of consolidative Docetaxel (75 mg/m2) given i.v. q21 days and Gefitinib 250 mg orally for 1 year or until disease progression. For radiation planning, the gross tumor volume (GTV) included the primary lesion as defined on contrast enhanced CT scan and lymph nodes involved with disease. Lymph nodes measuring .1.0 cm in short axis, necrotic or biopsy proven to contain metastatic disease were part of the GTV. 18Fluoro-deoxyglucose positron emission tomography was also used to aid in defining the GTV for both the primary lesion and draining lymph nodes. Treating the entire mediastinum electively was not allowed, but including the next echelon of mediastinal nodes beyond those that were clinically involved was permissible. Results: Beginning December 2003, 15 patients have been entered to determine the MTD of weekly Docetaxel when given concurrently with Gefitinib and thoracic radiation. The dose-limiting toxicities observed were primarily non-hematologic and occurred at dose level 3 (25 mg/m2). One patient experienced grade III esophagitis that resulted in grade III dehydration, a second patient experienced grade III diarrhea, and a third patient suffered a grade V interstitial pneumonitis, believed to be related to the Gefitinib. Fourteen of 15 patients completed the chemoradiation portion of the study and 2 patients completed all planned therapy. Four patients progressed during therapy, 3 patients discontinued treatment due to toxicity, and 2 patients refused to continue treatment. The median and 1-year survival thus far is 21 months and 56%, respectively. Conclusions: 70 Gy conformal thoracic radiation and concurrent Gefitinib/Docetaxel appears feasible but with modest toxicity. The study is currently enrolling patients at the weekly 20 mg/m2 Docetaxel dose level concurrent with 250 mg of daily Gefitinib. This study was supported in-part by Sanofi-Aventis and Astra Zeneca. Author Disclosure: A.W. Blackstock, Sanofi Aventis, B. Research Grant; Eli Lilly, B. Research Grant; Astra Zeneca, B. Research Grant; Merck, B. Research Grant; Genentech, B. Research Grant; Sanofi Aventis, F. Consultant/Advisory Board; Eli Lilly, F. Consultant/Advisory Board; C.A. Jensen, None; W.J. Petty, None; T. Oaks, None; M. Porosnicu, None; H. Clark, None; J.F. Lovato, None; A. Miller, None.
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Effects of Amifostine on Acute and Late Toxicity of Radiotherapy and Concurrent Chemotherapy for Local Advanced Non-Small Cell Lung Cancer
X. Wei, R. Komaki, P. K. Allen, V. P. Garza, Z. Liao, J. Y. Chang, T. M. Guerrero, S. D. Bilton, J. D. Cox The University of Texas M.D. Anderson Cancer Center, Houston, TX Purpose/Objective(s): To compare the acute and late toxicities of patients with local advance non-small-cell lung cancer (LANSCLC) treated by radiation treatment and concurrent chemotherapy with or without Amifostine. Materials/Methods: Clinical data were retrospectively analyzed for 193 LANSCLC patients treated with definitive three-dimensional conformal radiotherapy and concurrent chemotherapy from 1998 to 2006 at U.T. M.D. Anderson Cancer Center. 71 patients were on Amifostine group and 122 patients were on control group. Total dose at the isocenter was 60–70 Gy, 1.8–2.0 Gy/fx, 30–37
S476
Volume 69, Number 3, Supplement, 2007
Author Disclosure: L. Geng, None; A. Fu, None; D.E. Hallahan, NIH/NCI, R01-CA1256757, R21-CA128456, R01-CA112385, 2R01-CA89674, R01-CA88076, P50-CA90949, B. Research Grant.
2495
WITHDRAWN
2496
Gefitinib (ZD-1839) With Concurrent Docetaxel and Conformal Three-Dimensional Thoracic Radiation Followed by Consolidative Docetaxel/Gefitinib for Patients with Stage III NSCLC: A Phase I Study
A. W. Blackstock, C. A. Jensen, W. J. Petty, T. Oaks, M. Porosnicu, H. Clark, J. F. Lovato, A. Miller Wake Forest University, Winston-Salem, NC Purpose/Objective(s): The safety of 3-dimensional (3D) conformal thoracic radiation delivered with concurrent Gefitinib/Docetaxel chemotherapy in patients with inoperable stage III non-small cell lung cancer (NSCLC) has not been evaluated. In this phase I study we plan to determine the maximum tolerated dose (MTD) of weekly Docetaxel that can be safely delivered with concurrent Gefitinib and a definitive course of 3D conformal thoracic radiation. Materials/Methods: Patients with inoperable stage III NSCLC received weekly intravenous (i.v.) Docetaxel starting at a dose of 15 mg/m2 escalating to 30 mg/m2 in 5 mg/m2 increments and daily Gefitinib (250 mg given orally). Patients received concurrent thoracic radiation to a dose of 70 Gy utilizing 3D techniques. The chemoradiation therapy was followed by 2 cycles of consolidative Docetaxel (75 mg/m2) given i.v. q21 days and Gefitinib 250 mg orally for 1 year or until disease progression. For radiation planning, the gross tumor volume (GTV) included the primary lesion as defined on contrast enhanced CT scan and lymph nodes involved with disease. Lymph nodes measuring .1.0 cm in short axis, necrotic or biopsy proven to contain metastatic disease were part of the GTV. 18Fluoro-deoxyglucose positron emission tomography was also used to aid in defining the GTV for both the primary lesion and draining lymph nodes. Treating the entire mediastinum electively was not allowed, but including the next echelon of mediastinal nodes beyond those that were clinically involved was permissible. Results: Beginning December 2003, 15 patients have been entered to determine the MTD of weekly Docetaxel when given concurrently with Gefitinib and thoracic radiation. The dose-limiting toxicities observed were primarily non-hematologic and occurred at dose level 3 (25 mg/m2). One patient experienced grade III esophagitis that resulted in grade III dehydration, a second patient experienced grade III diarrhea, and a third patient suffered a grade V interstitial pneumonitis, believed to be related to the Gefitinib. Fourteen of 15 patients completed the chemoradiation portion of the study and 2 patients completed all planned therapy. Four patients progressed during therapy, 3 patients discontinued treatment due to toxicity, and 2 patients refused to continue treatment. The median and 1-year survival thus far is 21 months and 56%, respectively. Conclusions: 70 Gy conformal thoracic radiation and concurrent Gefitinib/Docetaxel appears feasible but with modest toxicity. The study is currently enrolling patients at the weekly 20 mg/m2 Docetaxel dose level concurrent with 250 mg of daily Gefitinib. This study was supported in-part by Sanofi-Aventis and Astra Zeneca. Author Disclosure: A.W. Blackstock, Sanofi Aventis, B. Research Grant; Eli Lilly, B. Research Grant; Astra Zeneca, B. Research Grant; Merck, B. Research Grant; Genentech, B. Research Grant; Sanofi Aventis, F. Consultant/Advisory Board; Eli Lilly, F. Consultant/Advisory Board; C.A. Jensen, None; W.J. Petty, None; T. Oaks, None; M. Porosnicu, None; H. Clark, None; J.F. Lovato, None; A. Miller, None.
2497
Effects of Amifostine on Acute and Late Toxicity of Radiotherapy and Concurrent Chemotherapy for Local Advanced Non-Small Cell Lung Cancer
X. Wei, R. Komaki, P. K. Allen, V. P. Garza, Z. Liao, J. Y. Chang, T. M. Guerrero, S. D. Bilton, J. D. Cox The University of Texas M.D. Anderson Cancer Center, Houston, TX Purpose/Objective(s): To compare the acute and late toxicities of patients with local advance non-small-cell lung cancer (LANSCLC) treated by radiation treatment and concurrent chemotherapy with or without Amifostine. Materials/Methods: Clinical data were retrospectively analyzed for 193 LANSCLC patients treated with definitive three-dimensional conformal radiotherapy and concurrent chemotherapy from 1998 to 2006 at U.T. M.D. Anderson Cancer Center. 71 patients were on Amifostine group and 122 patients were on control group. Total dose at the isocenter was 60–70 Gy, 1.8–2.0 Gy/fx, 30–37