Oxaliplatin combined with irinotecan and 5-fluorouracil/leucovorin (OCFL) in metastatic colorectal cancer: a phase I-II study

Background:: A phase I-II multicenter trial was conducted to define the maximal tolerated dose and describe the activity of an OCFL combination using oxaliplatin (OHP), irinotecan (CPT-11) and 5-fluorouracil (FU)/leucovorin (LV) in metastatic colorectal cancer (CRC). Patients and methods:: CRC patients not pretreated with palliative chemotherapy, with performance status ≤1 and adequate haematological, kidney and liver function, were eligible. Treatment consisted in weekly 24-h infusion 5-FU (2300 mg/m2)/LV (30 mg) and alternating OHP (70-85 mg/m2, days 1 and 15) and CPT-11 (80-140 mg/m2, days 8 and 22) repeated every 5 weeks. OHP and CPT-11 were escalated in cohorts of three to six patients. Results:: Thirty patients received a median of five cycles. Dose-limiting toxicity occurred at dose level 3, and the recommended dose was OHP 70 mg/m2, CPT-11 100 mg/m2, LV 30 mg and 5-FU 2300 mg/m2/24 h. Grade ≥3 toxicities were diarrhea 23%, neutropenia 20%, fatigue 7%, and neurologic 7%. Two febrile neutropenia episodes (one fatal) were recorded. Among 28 patients with measurable disease (90%), we observed two complete and 20 partial responses; overall RR was 78% (95% CI, 59% to 92%). Median time to progression and overall survival were 9.5 and 25.4 months, respectively. Seven patients underwent liver metastases resection. Conclusion:: OCFL is an overall well tolerated regimen with very high efficacy, which makes it most suitable for tumour control before surgery of metastatic diseas

Oxaliplatin combined with irinotecan and 5-fluorouracil/leucovorin (OCFL) in metastatic colorectal cancer: a phase I-II study

BACKGROUND: A phase I-II multicenter trial was conducted to define the maximal tolerated dose and describe the activity of an OCFL combination using oxaliplatin (OHP), irinotecan (CPT-11) and 5-fluorouracil (FU)/leucovorin (LV) in metastatic colorectal cancer (CRC). PATIENTS AND METHODS: CRC patients not pretreated with palliative chemotherapy, with performance status < or =1 and adequate haematological, kidney and liver function, were eligible. Treatment consisted in weekly 24-h infusion 5-FU (2300 mg/m(2))/LV (30 mg) and alternating OHP (70-85 mg/m(2), days 1 and 15) and CPT-11 (80-140 mg/m(2), days 8 and 22) repeated every 5 weeks. OHP and CPT-11 were escalated in cohorts of three to six patients. RESULTS: Thirty patients received a median of five cycles. Dose-limiting toxicity occurred at dose level 3, and the recommended dose was OHP 70 mg/m(2), CPT-11 100 mg/m(2), LV 30 mg and 5-FU 2300 mg/m(2)/24 h. Grade > or =3 toxicities were diarrhea 23%, neutropenia 20%, fatigue 7%, and neurologic 7%. Two febrile neutropenia episodes (one fatal) were recorded. Among 28 patients with measurable disease (90%), we observed two complete and 20 partial responses; overall RR was 78% (95% CI, 59% to 92%). Median time to progression and overall survival were 9.5 and 25.4 months, respectively. Seven patients underwent liver metastases resection. CONCLUSION: OCFL is an overall well tolerated regimen with very high efficacy, which makes it most suitable for tumour control before surgery of metastatic disease

Hepatic tocopherol content in primary hepatocellular carcinoma and liver metastases

The high incidence of hepatocellular carcinoma (HCC) in cirrhosis, where previous studies have indicated a severe reduction in several antioxidant vitamin factors, prompted us to compare plasma Liposoluble vitamins with tocopherol content in healthy and neoplastic liver tissue in humans. This, with a view to a more positive preventive dietary approach, given the conflicting results obtained by liposoluble vitamin dietary supplementation in different malignancies, Eleven patients with cirrhosis, 18 patients affected by cirrhosis with HCC, and 10 patients with liver metastases (LM) from digestive tract adenocarcinomas were compared with controls who had undergone perlaparoscopic cholecistectomy. Plasma alpha- and beta-carotene, retinol and tocopherol, together with liver tocopherol, from both nonmalignant portions and malignant nodules of the same organ, were determined by high-performance liquid chromatography following a well-assessed technique, The results confirm a trend towards a reduction in circulating carotenoids and tocopherol in cirrhosis and in patients affected by cirrhosis with HCC. Tocopherol content in liver tissue is significantly decreased in cirrhosis (0.26 +/- 0.03 mu mol/g prot., mean + SEM, P <.001) and in cirrhotic areas of the HCC group (0.31 + 0.02, P <.002), with respect to its content in liver specimens of healthy controls (0.46 + 0.03) and in healthy areas of the same organ in patients with LM (0.41 + 0.03). Tocopherol concentration is further reduced by 50% in malignant liver nodules of HCC, with respect to surrounding cirrhotic tissue, whereas in metastatic liver nodules from digestive neoplasms the tocopherol content is almost twice that of healthy surrounding areas. This unpredictable tocopherol behavior in liver specimens, of secondary as opposed to primary malignancies of the liver, affords further insight into the conflicting effects of liposoluble vitamins employed in the chemopreventive treatment of different malignant diseases, where hepatic tocopherol concentration show opposite trends: halved in primary HCC and doubled in LM of digestive adenocarcinomas, with respect to healthy controls

Reactivation of hepatitis B virus infection induced by interferon (IFN) in HBsAg-positive, antiHCV-positive patients.

Doses of IFN suitable for HCV may lead to reactivation of HBV infectio

EVIDENCE FOR HEPATITIS-B VIRUS-INFECTION IN PATIENTS WITH CHRONIC HEPATITIS-C WITH AND WITHOUT SEROLOGICAL MARKERS OF HEPATITIS-B

To assess the influence of HBV infection on anti-HCV-positive chronic liver disease, we performed a prospective case-control study comparing 19 HBsAg-positive, anti-HCV-positive patients with 38 HBsAg-negative, anti-HCV-positive patients, pair-matched for age, sex, and ALT levels. HBV and HCV infections were investigated by standard serology and polymerase chain reaction. HCV RNA was found in all patients with CAH and in 90.0% with cirrhosis (33% HBsAg-positive). HBV DNA sequences were found, in the HBsAg-positive subjects, in 71.4% of CAH and in 83.3% of cirrhotics; in the HBsAg-negative ones, only 10% of CAH but 77.7% of cirrhotics had demonstrable HBV DNA sequences. Consequently, 80.0% of cirrhotics had evidence of both HBV and HCV infection. Conventional serology gives partial information on the true occurrence of HBV infection in HBsAg-negative patients, while PCR defines more accurately the HBV status. When the rate of double infection is defined in this way, it correlates with the presence of cirrhosis

Pelvic osteoplasty in osteolytic metastases: Technical approach under fluoroscopic guidance and early clinical results

PURPOSE: To describe a new fluoroscopically guided technique for osteoplasty (or cementoplasty) of the superior and inferior pubic rami and ischial tuberosities and to provide information about the access routes and initial results on pain management after this technique. MATERIALS AND METHODS: Twenty-three lytic metastases of the superior and inferior pubic rami and ischial tuberosities were treated in 14 consecutive patients. Percutaneous access of the bones was performed under fluoroscopy. All patients had pain refractory to radiation and narcotic therapy and were unsuitable candidates for surgery according to multidisciplinary consensus. RESULTS: Technical success was achieved in all cases. Clinically, effective pain relief was obtained in 92% of patients. One intraarticular asymptomatic minor complication and one major complication resulting from leakage near the pudendal nerve were observed. The latter was subsequently treated by radiofrequency ablation. CONCLUSION: Pelvic osteoplasty appears to be a safe and highly effective palliative therapy for painful osteolytic malignant bone metastases

Pelvic osteoplasty in osteolytic metastases: Technical approach under fluoroscopic guidance and early clinical results

PURPOSE: To describe a new fluoroscopically guided technique for osteoplasty (or cementoplasty) of the superior and inferior pubic rami and ischial tuberosities and to provide information about the access routes and initial results on pain management after this technique. MATERIALS AND METHODS: Twenty-three lytic metastases of the superior and inferior pubic rami and ischial tuberosities were treated in 14 consecutive patients. Percutaneous access of the bones was performed under fluoroscopy. All patients had pain refractory to radiation and narcotic therapy and were unsuitable candidates for surgery according to multidisciplinary consensus. RESULTS: Technical success was achieved in all cases. Clinically, effective pain relief was obtained in 92% of patients. One intraarticular asymptomatic minor complication and one major complication resulting from leakage near the pudendal nerve were observed. The latter was subsequently treated by radiofrequency ablation. CONCLUSION: Pelvic osteoplasty appears to be a safe and highly effective palliative therapy for painful osteolytic malignant bone metastases