Sarcopenia is linked to treatment toxicity in patients with metastatic colorectal cancer.

Chemotherapy toxicity could be linked to decreased skeletal muscle (sarcopenia). We evaluated the effect of sarcopenia on chemotherapy toxicity among metastatic colorectal cancer (mCRC) patients. All consecutive mCRC patients in 3 hospitals were enrolled in this prospective, cross-sectional, multicenter study. Several nutritional indexes and scores were generated. Computed tomography (CT) images were analyzed to evaluate cross-sectional areas of muscle tissue (MT), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT). Toxicities were evaluated in the 2 mo following clinical evaluation. Fifty-one mCRC patients were included in the study. Sarcopenia was observed in 71% of patients (39% of women and 82% of men) whereas only 4% and 18% were considered as underweight using body mass index (BMI) or severely malnourished using the Nutritional Risk Index (NRI), respectively. Grade 3-4 toxicities were observed in 28% of patients. In multivariate analysis including age, sex, BMI, sarcopenia, SAT, and VAT, the only factor associated with Grade 3-4 toxicities was sarcopenia (odds ratio = 13.55; 95% confidence interval [1.08; 169.31], P = 0.043). In mCRC patients undergoing chemotherapy, sarcopenia was much more frequently observed than visible malnutrition. Despite the small number of patients included in our study, we found sarcopenia to be significantly associated with severe chemotherapy toxicity.

Gemcitabine plus oxaliplatin in advanced hepatocellular carcinoma: a large multicenter AGEO study.

BACKGROUND & AIMS: The current standard treatment for advanced hepatocellular carcinoma (HCC) is sorafenib. This drug is effective but generally does not induce tumor shrinkage and other treatment options are still needed. METHODS: This retrospective multicenter study included all consecutive patients with advanced HCC treated with gemcitabine and oxaliplatin (GEMOX) between 2001 and 2010. Survival curves were drawn with the Kaplan-Meier method and compared with the log-rank test. Univariate and multivariate analyses were used to evaluate prognostic factors. RESULTS: Two hundred four consecutive patients were treated with GEMOX (median age, 60 years; men, 86%; underlying cirrhosis, 76%). Grade 3-4 toxicity was observed in 44% of the patients (thrombocytopenia 24%, neutropenia 18%, diarrhea 14%, neurotoxicity 12%) leading to treatment discontinuation in 16% of the cases. The overall response and disease control rates were 22% (95% CI, 16-27) and 66% (95% CI, 59-72), respectively. No clinical or biological factors were associated with the treatment response, and 8.5% of the patients were subsequently eligible for curative-intent therapies after downstaging. Median PFS, TTP, and OS were 4.5 (95% CI, 4-6), 8 (95% CI, 6-11), and 11 months (95% CI, 9-14), respectively. In multivariate analysis, gender (p=0.03), underlying cirrhosis (p=0.01), CLIP score (p=0.03), and response to GEMOX (p<0.0001) were independently associated with OS. CONCLUSIONS: This large study confirms that GEMOX is effective with manageable toxicity in patients with advanced HCC. Tumor responses permitted potentially curative treatment that was not initially feasible in a significant proportion of patients.

Nutritional status affects treatment tolerability and survival in metastatic colorectal cancer patients: results of an AGEO prospective multicenter study.

BACKGROUND: The possible impact of malnutrition on the tolerability and efficacy of modern chemotherapy regimens for metastatic colorectal cancer (mCRC) is unclear. METHODS: In this prospective, cross-sectional, multicenter study, we collected demographic, oncological and nutritional data for all consecutive mCRC patients during a 14-day period in eight hospitals. Nutritional status was assessed with the nutritional risk index (NRI), and patients were classified as severely malnourished when NRI was <83.5; drug-induced toxicities were evaluated using the National Cancer Institute Common Toxicity Criteria (version 3.0). Survival times were calculated from the date of the nutritional assessment. RESULTS: We enrolled 114 mCRC patients (median age: 65 years, range: 22-92; WHO performance status 0/1/2/3: 21/54/21/4%) of whom 88% had at least 2 metastatic sites and 49% were receiving chemotherapy as first-line treatment. Malnutrition was diagnosed in 65% of the patients and was severe in 19%. Severe malnutrition was associated with more adverse effects following chemotherapy (p = 0.01) and with shorter median overall survival (14.0 vs. 36.2 months in non-/moderately malnourished patients, p = 0.02). CONCLUSIONS: In mCRC patients, severe malnutrition is associated with greater chemotherapy toxicity and reduced overall survival.

Post-fracture osteolysis of the pubic bone simulating a malignancy: report of a case.

Post-fracture osteolysis of the pubic bone is rare. We report a case of a 70-year-old woman with osteoporosis and a history of radiation therapy 2 years earlier. At presentation, she was found to have a bilateral sacral fracture and fractures of both pubic rami on one side. The pain persisted, and follow-up radiographs showed osteolysis of the pubic rami suggestive of metastatic disease. The development of a bony callus within 8 months established the diagnosis of benign osteolysis. About 50 cases of osteolysis at fracture sites have been reported to date, of which about a dozen occurred after radiation therapy. All the patients were elderly women with post-menopausal osteoporosis. Radiation therapy probably further increases the risk in this setting. The possibility of osteolysis at fracture sites in patients with osteoporosis should be borne in mind to avoid unnecessary and burdensome investigations that are costly and cause undue anxiety to the patients. Rest is the only effective treatment.

Gemcitabine plus oxaliplatin (GEMOX) in patients with advanced hepatocellular carcinoma (HCC): results of a phase II study.

BACKGROUND: New systemic therapies are needed to improve the prognosis of patients with advanced-stage hepatocellular carcinoma (HCC). In a Phase II trial involving previously untreated patients with advanced HCC, the more favorable schedule from a previous pilot study was evaluated. METHODS: Thirty-four patients with previously untreated advanced-stage HCC were prospectively enrolled. The GEMOX regimen consisted of gemcitabine 1000 mg/m(2) on Day 1 and oxaliplatin 100 mg/m(2) on Day 2. The treatment was repeated every 2 weeks until disease progression or limiting toxicity. RESULTS: Thirty-two patients were assessable for efficacy and 33 for toxicity. In all, 323 treatment cycles were administered. No toxic deaths occurred. Hematological grade 3-4 toxicity consisted of thrombocytopenia (27% of patients) and neutropenia (24%), including 2 febrile neutropenia and anemia (9%). Grade 3 oxaliplatin-induced neurotoxicity was observed in 3 (9%) patients. The overall response rate was 18% (95% confidence interval [CI]: 8-34) and disease stabilization was observed in 58% of patients (including 5 minor responses), giving a disease control rate of 76%. Median progression-free and overall survival times were, respectively, 6.3 months (95% CI: 4.3-10.1 months) and 11.5 months (95% CI: 8.5-14.3 months). Treatment was significantly more effective in patients with nonalcoholic cirrhosis than in those with alcoholic cirrhosis. CONCLUSIONS: The GEMOX regimen seems to be well tolerated and active in advanced HCC, especially in patients with underlying nonalcoholic liver disease. A Phase II study of the GEMOX regimen plus cetuximab is ongoing.

[Oxaliplatin in gastro-intestinal tract cancer except colorectal cancer]. / Oxaliplatine en oncologie digestive en dehors du cancer colorectal.

In a few years, oxaliplatin became a standard treatment of colorectal cancer not only in metastatic situation but also in the adjuvant setting. In the others gastro-intestinal malignancies such as oesophageal, stomach, pancreatic, liver and biliary tract cancers, the effectiveness of the current chemotherapies is unfortunately most often disappointing. Several teams thus decided to evaluate oxaliplatin, essentially in polychemotherapy regimens and sometimes in combination with radiotherapy. Many clinical trials are in progress, others will begin soon. Nevertheless, the results of the first studies already presented are promising, especially the gemcitabine and oxaliplatin combination on 2 days schedule in treating patients with advanced pancreatic, biliary tract and the fluoropyrimidine and oxaliplatin in treating patients with advanced gastric cancer.

Gemcitabine plus oxaliplatin for patients with advanced hepatocellular carcinoma using two different schedules.

BACKGROUND: New therapies are needed to improve the prognosis of patients with advanced hepatocellular carcinoma (HCC). Various gemcitabine-oxaliplatin combinations have been tested recently in patients with ovarian and pancreatic carcinoma, yielding interesting results with little toxicity. Therefore, the authors evaluated the activity and toxicity of two such combinations in patients with HCC. METHODS: Twenty-one patients were enrolled prospectively in the study. Eleven patients received gemcitabine 1000 mg/m2 on Day 1 and oxaliplatin 100 mg/m2 on Day 2 (GEMOX-1), and 10 patients received gemcitabine 1500 mg/m2 on Day 1 followed by oxaliplatin 85 mg/m2 on Day 1 (GEMOX-2). Treatment was repeated every 2 weeks until disease progression developed or until unacceptable adverse effects occurred. RESULTS: All patients were assessable for response and toxicity. Four patients (19%) achieved objective responses (95% confidence interval, 13-26%), including 3 patients in the GEMOX-1 group and 1 patient in the GEMOX-2 group. Ten patients (48%) had stable disease, and 7 patients (33%) experienced disease progression. The median progression-free survival was 5 months, and the median overall survival was 12 months. Fifty-four percent of patients in the GEMOX-1 group and 50% of patients in the GEMOX-2 group had received previous systemic chemotherapy or cisplatin-based chemoembolization. Grade 3-4 hematologic toxicity, according to National Cancer Institute Common Toxicity Criteria, consisted of thrombocytopenia (GEMOX-1 vs. GEMOX-2, 18% vs. 40%) and neutropenia (0% vs. 30%). No Grade 3-4 nonhematologic toxicity was observed, except for 1 episode of Grade 3 diarrhea. Grade 1 neurotoxicity and Grade 2 neurotoxicity (specific scale), respectively, were observed in 4 patients and 7 patients receiving GEMOX-1 and in 7 patients and 1 patient receiving GEMOX-2. CONCLUSIONS: Gemcitabine-oxaliplatin combination therapy is feasible in patients with advanced HCC. The GEMOX-1 regimen was tolerated better than the GEMOX-2 regimen. Currently, the GEMOX-1 regimen is being evaluated in a Phase II study in previously untreated patients with HCC.