TY - JOUR
T1 - Induction and concurrent paclitaxel/carboplatin every 3 weeks with thoracic radiotherapy in locally advanced non-small-cell lung cancer
T2 - An interim report
AU - Movsas, Benjamin
AU - Hudes, Richard S.
AU - Schol, Jessie
AU - Millenson, Michael
AU - Rosvold, Elizabeth
AU - Nicolaou, Nicholas
AU - Litwin, Samuel
AU - Wang, Hao
AU - Keenan, Eileen
AU - Curran, Walter J.
AU - Langer, Corey J.
N1 - Funding Information:
This study was supported by a grant from Amgen. The authors wish to thank Louise Marcewicz for her excellent secretarial assistance in the preparation of this manuscript.
PY - 2001/11
Y1 - 2001/11
N2 - The paclitaxel/carboplatin combination has demonstrated promising activity in metastatic non-small-cell lung cancer (NSCLC); therefore, we mounted an exploratory study of these agents with thoracic radiation (TRT) in locally advanced NSCLC. Eligibility stipulated a Karnofsky performance status ≥ 70%, weight loss ≤ 5%, and primarily stage IIIB or bulky IIIA NSCLC. Induction chemotherapy (CT), 2 cycles of paclitaxel 175-225 mg/m2 over 3 hours and carboplatin (targeted area under the curve [AUC] of 7.5), was administered on days 1 and 22. Granulocyte colony-stimulating factor (G-CSF) 5 μg/kg was given on days 2-15 and 23-36 to all patients; half were randomized to priming G-CSF every day × 5 prior to day 1 of induction therapy. On day 43, TRT (60-63 Gy/30-34 fx) was initiated. At dose level 1, only Fox Chase Cancer Center patients received carboplatin (initial target AUC 3.75) and paclitaxel (67.5 mg/m2 over 3 hours) days 43 and 64. In the absence of dose-limiting toxicity, phase I dose escalation in 3-patient cohorts was scheduled to proceed to a maximum carboplatin AUC 7.5 and paclitaxel dose of 210 mg/m2. To date, 53 patients have received induction therapy; 4 are too early to evaluate. The portion of the study evaluating G-CSF priming revealed no myeloprotective effect, likely due to a lack of myelosuppressive toxicity with the conventionally dosed cohort. Twenty-two patients have received concurrent TRT/CT. In sequential cohorts, the chemotherapy doses on days 43 and 64 have been escalated (to paclitaxel 175 mg/m2 and carboplatin AUC 5) with 1 episode each of grade 4 granulocytopenia and grade 3 anemia. The occurrence of grade ≥ 2 esophagitis has corresponded to length (> 16 cm) of esophagus in the radiation treatment field (Fisher's exact test, P = 0.006). The partial response rate to induction therapy was 40% and to the combined modality therapy was 60%. The median survival for all 49 patients is 15.3 months, with a median disease-free survival (DFS) of 7.8 months. In the subset of 22 patients treated on the phase I portion of the study, the median survival and DFS were 18.5 months and 13.5 months, respectively. Induction therapy with paclitaxel and carboplatin followed by concurrent chemoradiotherapy with the same agents is an active and well-tolerated treatment approach in locally advanced NSCLC. To date, paclitaxel 175 mg/m2 plus carboplatin AUC 5 administered at 3-week intervals for 2 cycles is safe in combination with TRT.
AB - The paclitaxel/carboplatin combination has demonstrated promising activity in metastatic non-small-cell lung cancer (NSCLC); therefore, we mounted an exploratory study of these agents with thoracic radiation (TRT) in locally advanced NSCLC. Eligibility stipulated a Karnofsky performance status ≥ 70%, weight loss ≤ 5%, and primarily stage IIIB or bulky IIIA NSCLC. Induction chemotherapy (CT), 2 cycles of paclitaxel 175-225 mg/m2 over 3 hours and carboplatin (targeted area under the curve [AUC] of 7.5), was administered on days 1 and 22. Granulocyte colony-stimulating factor (G-CSF) 5 μg/kg was given on days 2-15 and 23-36 to all patients; half were randomized to priming G-CSF every day × 5 prior to day 1 of induction therapy. On day 43, TRT (60-63 Gy/30-34 fx) was initiated. At dose level 1, only Fox Chase Cancer Center patients received carboplatin (initial target AUC 3.75) and paclitaxel (67.5 mg/m2 over 3 hours) days 43 and 64. In the absence of dose-limiting toxicity, phase I dose escalation in 3-patient cohorts was scheduled to proceed to a maximum carboplatin AUC 7.5 and paclitaxel dose of 210 mg/m2. To date, 53 patients have received induction therapy; 4 are too early to evaluate. The portion of the study evaluating G-CSF priming revealed no myeloprotective effect, likely due to a lack of myelosuppressive toxicity with the conventionally dosed cohort. Twenty-two patients have received concurrent TRT/CT. In sequential cohorts, the chemotherapy doses on days 43 and 64 have been escalated (to paclitaxel 175 mg/m2 and carboplatin AUC 5) with 1 episode each of grade 4 granulocytopenia and grade 3 anemia. The occurrence of grade ≥ 2 esophagitis has corresponded to length (> 16 cm) of esophagus in the radiation treatment field (Fisher's exact test, P = 0.006). The partial response rate to induction therapy was 40% and to the combined modality therapy was 60%. The median survival for all 49 patients is 15.3 months, with a median disease-free survival (DFS) of 7.8 months. In the subset of 22 patients treated on the phase I portion of the study, the median survival and DFS were 18.5 months and 13.5 months, respectively. Induction therapy with paclitaxel and carboplatin followed by concurrent chemoradiotherapy with the same agents is an active and well-tolerated treatment approach in locally advanced NSCLC. To date, paclitaxel 175 mg/m2 plus carboplatin AUC 5 administered at 3-week intervals for 2 cycles is safe in combination with TRT.
KW - Carboplatin
KW - G-CSF
KW - Induction chemoradiation
KW - Paclitaxel
KW - Thoracic radiotherapy
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UR - http://www.scopus.com/inward/citedby.url?scp=0035214295&partnerID=8YFLogxK
U2 - 10.3816/CLC.2001.n.023
DO - 10.3816/CLC.2001.n.023
M3 - Article
C2 - 14659027
AN - SCOPUS:0035214295
SN - 1525-7304
VL - 3
SP - 125
EP - 132
JO - Clinical lung cancer
JF - Clinical lung cancer
IS - 2
ER -