A phase II trial of concurrent chemoradiotherapy with weekly paclitaxel and carboplatin in advanced oesophageal carcinoma.

BACKGROUND: This study was performed to assess the efficacy and feasibility of definitive chemoradiotherapy consisting of weekly doses of combined paclitaxel and carboplatin concurrent with radiation therapy, followed by 2 cycles of consolidation chemotherapy for advanced esophageal carcinoma. METHODS: Eligibility criteria included local, advanced, newly diagnosed and postoperative local regional lymph node metastasis; Eastern Cooperative Oncology Group (ECOG) score ≤ 2; and adequate organ function. Patients received concurrent chemoradiation therapy consisting of radiotherapy (50.4 Gy/28 Fx or 61.2 Gy/34 Fx) and concurrent paclitaxel (50 mg/m2) and carboplatin (area under the curve, AUC = 2) on days 1, 8, 15, 22 and 29. The two-cycle consolidation chemotherapy protocol was paclitaxel (175 mg/m2) plus carboplatin (AUC = 5) administered on days 57 and 85, after concurrent chemoradiotherapy. RESULTS: Between August 2013 and February 2015, 65 patients with oesophageal carcinoma were enrolled in the study; 34 (52.3%) were newly diagnosed and 31 (47.6%) had postoperative local regional lymph node metastasis. The median overall survival time was 21.7 months (95% confidence interval [CI] 16.7-26.6), and the median progression-free survival time was 12.1 months (95% CI 9.0-15.3). A total of 96.9% (63/65) and 67.6% (44/65) patients completed ≥5 cycles and all 7 cycles of chemotherapy, respectively. A total of 93.8% (61/65) patients completed radiation therapy. The 1- and 2-year overall survival rates were 73.7 and 42.0%, respectively. The 1- and 2-year progression-free survival rates were 50.6 and 31.1%, respectively. Grade 3-4 toxicity during chemoradiotherapy included neutropenia (24.5%), thrombocytopenia (4.6%), fatigue (1.5%), anaemia (1.5%), radiation dermatitis (1.5%), pneumonitis (1.5%), oesophagitis (4.6%) and vomiting (1.5%). CONCLUSIONS: In patients with locally advanced oesophageal cancer, the combination of weekly doses of paclitaxel and carboplatin was well tolerated and produced comparable results. A three-arm randomised phase III trial (NCT02459457) comparing paclitaxel in combination with cisplatin, carboplatin or 5-fluorouracil with concurrent radiotherapy is on-going at our hospital.

A phase II study of concurrent chemoradiotherapy combined with a weekly paclitaxel and 5-fluorouracil regimen to treat patients with advanced oesophageal carcinoma.

BACKGROUND: A phase II study was performed to investigate the safety and efficacy of weekly doses of combined paclitaxel and 5-fluorouracil (5-FU) with concurrent radiation therapy, followed by 2 cycles of consolidation chemotherapy to treat patients with advanced oesophageal carcinoma. METHODS: The eligibility criteria included local, advanced, newly diagnosed and postoperative local regional lymph node metastasis; an Eastern Cooperative Oncology Group (ECOG) score of ≤ 2; and adequate organ function. Patients received chemoradiotherapy consisting of radiotherapy (50.4 Gy/28 Fx or 61.2 Gy/34 Fx) and concurrent paclitaxel (50 mg/m2) and 5-FU (300 mg/m2) for 96 h on days 1, 8, 15, 22, and 29. The two-cycle consolidation chemotherapy protocol included paclitaxel (175 mg/m2) plus continuously infused 5-FU (1800 mg/m2) for 72 h administered on days 57 and 85, after concurrent chemoradiotherapy. RESULTS: Between February 2012 and August 2013, 53 patients with oesophageal carcinoma were enrolled in the study. Among these patients, 33 (62.2%) were newly diagnosed and 20 (37.7%) had postoperative local regional lymph node metastasis. The median overall survival (OS) time was 17.9 months (95% CIs = 11.9-23.9), and the median progression-free survival (PFS) time was 12.4 months (95% CIs = 8.6-16.1). Approximately 84.9% (45/53) and 50.9% (27/53) of the patients completed ≥ 5 cycles and all 7 cycles of chemotherapy, respectively. Approximately 86.7% (46/53) of patients completed radiation therapy. The 1-, 2-, and 3-year OS rates were 66.0%, 37.7%, and 35.8%, respectively. The 1-, 2-, and 3-year local control rates were 76.9%, 66.4%, and 66.4%, respectively. Seventeen patients (32%) experienced grade 3 or higher toxicity. Grade 3 to 5 toxicity during chemoradiotherapy included neutropaenia (7.5%), thrombocytopaenia (1.8%), fatigue (7.5%), anaemia (1.8%), dermatitis radiation (1.8%), pneumonitis (5.6%), oesophagitis (9.4%) and vomiting (3.7%). CONCLUSIONS: The combination of weekly doses of paclitaxel and 5-FU was well tolerated and produced comparable results among patients with locally advanced oesophageal cancer. A randomised phase III trial (NCT01591135) comparing paclitaxel plus 5-FU with cisplatin plus 5-FU is on-going at our hospital.

Long-term results of paclitaxel plus cisplatin with concurrent radiotherapy for loco-regional esophageal squamous cell carcinoma.

AIM: To evaluate the long-term effectiveness and late toxicities of paclitaxel (PTX) plus cisplatin (DDP) with concurrent radiotherapy for locally advanced esophageal squamous cancer. METHODS: Between 2008 and 2011, 76 patients were enrolled in a phase II study on the treatment of loco-regionally advanced esophageal cancer with radiotherapy (68.4 Gy/44 fractions or 61.2 Gy/34 fractions) combined with 4-cycle chemotherapy consisting of DDP (25 mg/m2 per day for 3 d) and PTX (175 mg/m2 for 3 h). The primary endpoints were overall survival and progression-free survival, and the secondary endpoints were toxicity and the treatment failure pattern. RESULTS: A total of 76 patients were enrolled in this study, of whom 63.2% finished the whole regimen. The 5-year survival rates for the per-protocol population and intent-to-treat population were 25.4% and 26.4%, respectively, and the median survival rates were 23.7 mo and 28.5 mo, respectively. Grade 3 or 4 late toxicity was observed in only one patient (heart failure). In log-rank analysis, the pretreatment stage (stage II + III: 36.1 mo vs stage IV: 14.9 mo) and the completed cycle (1-3 cycles: 16.1 mo vs 4 cycles: 35.5 mo) were significant prognostic factors (P = 0.037 < 0.05 and P = 0.013 < 0.05). CONCLUSION: Radiotherapy combined with chemotherapy consisting of PTX and DDP is a safe and effective definitive treatment for loco-regionally advanced esophageal squamous cancer.