Mansoura randomized trial: Irinotecan/de gramont regimen versus de gramont regimen alone in chemotherapy naive matastic colorectal carcinoma

The mainstay of treatment for metastatic colorectal carcinoma is chemotherapy. The De Gramont regimen [high-dose leucovorin [LV] and fluorouracil [5-FU] bolus plus continuous infusion every 2 weeks] had been proved to be superior to the standard North Central Cancer Treatment Group/Mayo Clinic 5 day bolus 5-FU/LV regimen in the metastatic state. Irinotecan [CPT-11], a semi-synthetic derivative ofcamp-tothecin, has been shown to exert a cytotoxic action in colorectal carcinoma via the potent and specific inhibition of the nuclear enzyme DNA topoisomerase 1. Investigating the difference in response, toxicity, progression-free and overall survival between the de Gramont regimen alone and the irinotecan plus the de Gramont regimen in the management of cases of metastatic colorectal carcinoma in our locality 160 patients with metastatic colorectal carcinoma were referred mainly from the Gastro Enterology Center [GEC] to both the Clinical Oncology and Nuclear Medicine Department and the Oncology Center of Mansoura University and randomized to receive a 2-hour infusion of LV [200mg/m2/d] followed by a 5-FU bolus [400mg/m2/d] and 22-hour infusion [600mg/m2/d] for 2 consecutive days every 2 weeks, either alone [group A] or together with irinotecan [180mg/m2, 30min intravenous infusion] on day 1 [group B]. Median follow up period was 15 months. Patients allocated to the irinotecan/deGramont regimen had statistically better response rate and symptom amelioration [p=0.04]. Moreover, improvement of patients weight and performance status were statistically better in group B [p=0.03 and 0.02 respectively]. Concerning survival figures, group B had statistically better median progression free survival [8 versus 5 months respectively] and better median overall survival [17 versus 14 months respectively] [p=0.00 and 0.01 respectively]. As regard toxicity, both diarrhea and neutropenia of grade 3 and 4 were more encountered in group B [p=0.004 and 0.003 respectively. free survival were receiving irinotecan, good performance status and normal levels of both hemoglobin and white blood cell count at presentation. On the other hand, independent favorable prognostic factors affecting overall survival were good performance status receiving irinotecan, limited number of metastatic foci and normal levels of hemoglobin, white blood cell count and alkaline phosphatase at presentation. The benefit of adding irinotecan to the de Gramont regimen was reflected positively on all the end points as response, progression-free and overall survival. In addition, the toxicity is generally tolerable and manageable. It is clear that performance status, the number of metastatic foci, and the level of each of hemoglobin, white blood cell count and alkaline phosphatase at time of presentation had their prognostic effect on the course of metastatic colorectal carcinoma

Oral capecitabine in combination with gemcitabine in management of advanced pancreatic carcinoma

Preclinical studies indicate positive biochemical and synergistic effects between capecitabine, an oral fluorouracil, and gemcitabine, the standard treatment for advanced pancreatic cancer [APC]. The goals of this study were to investigate the efficacy and safety of such combination for patients with APC. Twenty-two eligible patients with APC were treated with oral capecitabine and gemcitabine [CapGem regimen]. Capecitabine was given in a dose of 750 mg/m2 BID daily from day 1 to day 14 followed by one-week rest. Gemcitabine was given on day 1 and day 8 in a dose of 1000 mg/m2/dose given as i.v. infusion in 250 ml normal saline for 30 minutes of each 3-week cycle. Tumor lesions were assessed for objective response by physical examination and abdominal CT every two cycles of chemotherapy. Adverse events were monitored continuously during treatment and for one month after the last dose of the study. Estimation of survival was done every two months alter completion of chemotherapy cycles. The results revealed that among the 22 studied patients, two patients achieved complete clinical response [9.1%] and five patients [22.7%] achieved partial response with overall objective response rate 31.8% [95% CI, 0.21 to 0.39]. The median response duration of all responders was 31 weeks [95% CI, 18 to 39 weeks]. CA-19-9 was dropped >50% in eight patients and dropped >90% in five patients. The median time to disease progression in all 22 patients was 32 weeks [95% CI, 21 to 40 weeks]. The median survival for the whole studied group was 36 weeks [95% CI, 27 to 48 weeks]. Treatment was generally well tolerated in the outpatient settings. In conclusion, capecitabine in combination with gemcitabine was well tolerated regimen with apparent efficacy in patients with APC. Therefore, the supra-additive antitumor effect of such combination regimen of CapGem plus the advantage of oral administration of capecitabine merits this protocol promising