Safety Of Neoadjuvant Chemoradiotherapy Research Articles

Preoperative chemoradiotherapy with docetaxel, doxifluridine, and low-dose cisplatin for stage II/III squamous cell carcinoma of the esophagus

Preoperative chemotherapy using 5-fluorouracil and cisplatin is a standard treatment for stage II/III esophageal squamous cell carcinoma (ESCC) in Japan. However, stronger therapies are needed for advanced ESCC. This retrospective study aimed to evaluate the feasibility and safety of neoadjuvant chemoradiotherapy with R-DDP. Patients diagnosed with clinical stage II/III ESCC and initially treated with preoperative R-DDP were enrolled. R-DDP comprised intravenous docetaxel (40 mg m−2 day−1 on day 1), oral doxifluridine (800 mg m−2 day−1 on days 1–7), low-dose cisplatin (5 mg m−2 day−1 on days 1–5), and concurrent radiation (2 Gy day−1 on days 1–5), which were repeated weekly for 3 weeks (maximum total radiation: 30 Gy). If clinical stage T4 was suspected, another week of the regimen was added (maximum total radiation: 40 Gy). After therapy evaluation, patients underwent esophagectomy with 2 or 3 fields of lymphadenectomy. Between April 2003 and March 2011, 19 eligible patients were enrolled (treatment completion rate: 89.5 %). Complete or partial response was obtained in 17 cases (89.5 %), and 8 cases (42.1 %) involved downstaging. In resected specimens, the primary tumor’s histopathological grade was 1, 2, and 3 in 3, 11, and 5 cases. Although 42.1 % of patients developed grade 3+ adverse events, there were no severe perioperative complications. Three- and five-year overall survival rates were 42.1 and 36.1 %, with a 23-month median progression-free survival. Although this treatment had good antitumor effects, it did not necessarily confer prognostic improvements. R-DDP could become a therapeutic strategy for locally advanced ESCC.

Neoadjuvant chemoradiotherapy with S-1 in patients with borderline resectable pancreatic cancer.

302 Background: The aim of this study was to investigate the efficacy and safety of neoadjuvant chemoradiotherapy (NACRT) with S-1 (oral fluoropyrimidine) followed by surgery for the treatment of borderline resectable pancreatic cancer that involved the major visceral artery or the portal venous system. Methods: Twenty-eight patients with pancreatic cancers that abutted the SMA in 10, the CHA in 7, the both SMA and CHA in 1, and occluded the SMV/PV in 10 were treated with NACRT at a single institution. Radiation therapy was delivered at a total dose of 50.4 Gy in 28 fractions. S-1 was administered orally at a dose of 80 mg/m(2)/day for 14 consecutive days followed by a 7-day rest period during radiation therapy. After radiotherapy and 2 courses of S-1, restaging was done to evaluate secondary resectability. Results: Of the all patients, 25 underwent a full course of NACRT, and NACRT terminated in 3 patients because of grade 3 leukopenia in 2 and tumor bleeding in 1. Partial response was achieved in 3 patients and stable disease in 22. Twenty-four patients (86%) underwent surgical resection, and all had margin-negative (R0) resections. Only two patients (8%) had major morbidity as Clavien-Dindo’s classification III or more, and there was no operative or in-hospital mortality. Pathological examination revealed that more than 50% of tumor cells had disappeared in 14 cases and all cases achieved Evans’ score IIa and more. Conclusions: Neoadjuvant chemoradiation with S-1 was feasible and promising therapy for borderline resectable pancreatic cancer that involves the major artery or the portal venous system.

Pilot Feasibility Study of Neoadjuvant Chemoradiotherapy with S-1 in Patients with Locally Advanced Gastric Cancer Featuring Adjacent Tissue Invasion or JGCA Bulky N2 Lymph Node Metastases

To improve the prognosis of locally advanced gastric cancer, clinical trials of neoadjuvant chemotherapy (NAC) are being performed. Although neoadjuvant chemoradiotherapy (NACRT) generally achieves superior local tumor control to NAC, its efficacy for locally advanced gastric cancers remains unclear. Therefore, a prospective trial was conducted to explore the feasibility and safety of NACRT with oral S-1 in a series of cases. Patients who had Japanese Gastric Cancer Association (JGCA) cStage IIIB gastric cancer were enrolled onto this study and received oral S-1 (65 mg/m(2)/day) administration and 50-Gy radiotherapy followed by radical surgery. The primary end points were completion of therapy and safety. Between October 2005 and September 2008, 12 eligible patients were enrolled. Two could not complete the chemotherapy because of grade 3 toxicity. R0 resections were performed in 11 patients (91.7 %) (95 % confidence interval 61.5-99.8). Although operative morbidity was observed in two cases, there were no postoperative deaths. A pathologic response was observed in 10 patients (83.3 %). In five (62.5 %) of eight gastric cancers with invasion to adjacent structures, microscopic tumor deposits were not found in the affected organs. The 3-year survival rate was 58.3 % during a median follow-up period of 36 months. Although this study is preliminary, the present regimen seems to be feasible and safe as a treatment for locally advanced gastric cancers featuring adjacent tissue invasion or JGCA bulky N2 disease. This treatment approach should now be tested using the new tumor, node, metastasis staging system in a large clinical trial.

A phase II study of neoadjuvant chemoradiotherapy with oxaliplatin and capecitabine for rectal cancer

Purpose This study evaluated the efficacy and safety of neoadjuvant chemoradiotherapy with the XELOX regimen in rectal cancer patients. Patients and methods Twenty-five patients with histopathologically confirmed and locally advanced rectal cancer (T3/T4 or N+) were enrolled in the study. Radiotherapy of 5000 cGy was delivered in 25 fractions of 200 cGy five times per week for a total of 5 weeks. During the first, second, fourth and fifth weeks of radiotherapy, the patients also received the following chemotherapy: 50 mg/m 2 oxaliplatin on day one and 850 mg/m 2 capecitabine bid for 5 days. Surgery was scheduled 5–6 weeks after the completion of the preoperative chemoradiotherapy. Four weeks after the surgery, four more cycles of chemotherapy were administered every 3 weeks. The postoperative chemotherapy consisted of 130 mg/m 2 oxaliplatin on day 1 and 1000 mg/m 2 capecitabine bid from day 1 to day 14. The end points were the downstage rate, R0 resection rate, and sphincter preservation rate. Results Twenty-five patients received the neoadjuvant chemoradiotherapy. The overall regression rate was 85%, with a Grade 3/4 regression rate of 30% and a pathological complete response rate of 12%. Among the 17 patients with lower rectal cancer, thirteen (76%) were originally indicated for abdominal–perineal resection (APR). However, after the neoadjuvant chemoradiotherapy, the anus could be preserved in nine patients (53%). The most frequent toxicities of the chemoradiotherapy were diarrhea (64%) and hematological toxicity (60%), followed by nausea and vomiting (48%), urinary tract irritation (28%), and anal pain (24%). Grade 3 or 4 adverse events were relatively infrequent and presented as diarrhea (12%), myelosuppression (8%), and elevated transaminase (4%). Six cases also experienced long-term anal exudates after surgery. Conclusions Neoadjuvant chemoradiotherapy using the XELOX regimen in rectal cancer patients obviously reduced the TNM staging and improved the pathological complete response rate. The therapy was well-tolerated and had mild adverse events and no serious perioperational complications.