Safety and Feasibility of Carboplatin and Paclitaxel followed by Fluoropyrimidine Analogs and Radiation as Adjuvant Therapy for Gastric Cancer

Background: Adjuvant 5-fluorouracil (5FU)-based chemo-radiotherapy is currently considered a standard of care for the treatment of gastric cancer. The impact of 5FU-based adjuvant therapy on the rate of distant recurrence has been modest. In order to improve the systemic effects of adjuvant therapy, we have been treating patients with resected gastric cancer with carboplatin and paclitaxel followed by fluoropyrimidine analogue and radiation. Methods: We report on the outcomes of 21 consecutive gastric cancer patients treated off protocol with adjuvant carboplatin (area under the curve 5 mg/ml × min) and paclitaxel (175–200 mg/m2) every 3 weeks, followed by concurrent pyrimidine analogs (either capecitabine 1,600–2,000 mg/m2/day in 17 patients, or 5FU 200 mg/m2/day in 4 patients) and radiation (45–50.4 Gy). Patients received a total of 4–6 cycles of carboplatin and paclitaxel. Results: The median age at diagnosis was 60 years. Sixteen patients had stage 3 disease and 7 of them had positive surgical margins (6 with R1 and 1 with R2 resection), 3 patients were stage 2, and 2 patients were stage 1 (all had R0 resection). All patients had D1/D2 (4 had D2 and 17 had D1) lymph node dissection. The incidence of grade 3 or higher overall, hematologic, or gastrointestinal toxicity in the patients receiving carboplatin and paclitaxel was 57, 48 and 10%, respectively. No treatment-related deaths were observed. After adjuvant treatment 15 patients developed recurrent disease, 10 of whom had distant metastases. The median recurrence-free survival (RFS) was 12.3 months. The median overall survival (OS) was 16.0 months. Patients with R0 resection had significantly longer OS than did those with positive surgical margins (log-rank p = 0.0060). Median OS for the R0 resection group was 28.8 months. Conclusions: Carboplatin and paclitaxel added to radiation plus fluoropyrimidine analogs is a well-tolerated regimen in the adjuvant setting. The activity of this regimen in this relatively high-risk group of gastric cancer patients is of interest for future development

CA19-9 as a predictor of tumor response and survival in patients with advanced pancreatic cancer treated with gemcitabine based chemotherapy

The aim of this study was to determine the predictive role of pretreatment carbohydrate antigen 19-9 (CA19-9) measurement and its change after one cycle of gemcitabine-based therapy for response, time to progression (TTP) and overall survival (OS).Analyses were derived from three consecutive gemcitabine-containing phase II clinical trials between 1997 and 2004.A total of 111 patients with pancreas cancer was studied. Baseline CA19-9 concentrations were dichotomized near the median. Lower baseline CA19-9 levels were positively associated with OS (median 9.1 vs 6.1 months, P  = 0.0057) and TTP (median 6.4 vs 4.2 months, P  = 0.0044).The covariate adjusted hazard ratio (HR) for progression among patients with baseline CA19-9 ≥ 1000 ng/mL was HR = 1.94 (95% CI 1.24–3.02), with P  = 0.0035. The covariate adjusted risk of death among patients with baseline CA19-9 ≥ 1000 ng/ml was similarly elevated: HR = 1.90 (95% CI 1.23–2.94), with P  = 0.0039. Change in CA19-9 levels from baseline to the end of treatment cycle 1 did not predict objective response ( P  = 0.75). There was somewhat longer OS (median 8.7 vs 7.1 months) and TTP (median 7.1 vs 5.4 months) in patients with ≥50% reduction in serum CA19-9 concentrations, but this was not statistically significant ( P  = 0.74 and 0.81, respectively).Baseline CA19-9 levels may predict survival in patients with advanced pancreas cancer. The change in CA19-9 levels determined within 1 month of the initiation of therapy did not predict treatment outcome.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/79310/1/j.1743-7563.2010.01290.x.pd

A Phase II study of celecoxib, gemcitabine, and cisplatin in advanced pancreatic cancer

Background . Pancreatic cancer is amongst the most chemoresistant malignancies. Expression of the cyclooxygenase-2 (COX-2) enzyme plays a major role in tumor progression and resistance to therapy. A Phase II study was undertaken to determine the effect of gemcitabine by fixed-dose rate infusion (FDR), cisplatin and the COX-2 inhibitor, celecoxib, on the 6-month survival rate in patients with metastatic pancreatic cancer.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45281/1/10637_2005_Article_1028.pd