Quality of life during first-line FOLFOX4±panitumumab in RAS wild-type metastatic colorectal carcinoma : results from a randomised controlled trial

Metastatic colorectal cancer is rarely curable. Improving quality of life is therefore a key treatment goal. We report quality of life for patients with RAS wild-type metastatic colorectal cancer in the PRIME study. A randomised phase 3 open-label study of first-line panitumumab+FOLFOX4 vs FOLFOX4 enrolled adults with untreated metastatic colorectal cancer and an Eastern Cooperative Oncology Group performance status of 0-2. This analysis includes patients with wild-type RAS tumours (n=505). Quality of life (prespecified end point) was assessed using the EuroQoL 5-domain health state index and overall health rating in all patients and by early tumour shrinkage status (≥30% reduction in size by week 8; exploratory end point). Differences in quality of life were assessed using analysis of covariance and a mixed-effect piecewise linear model, and were also analysed by skin toxicity severity. There were no statistically significant differences between treatment arms from baseline to progression or to discontinuation. Grade 3+ skin toxicity was reported by 38% of patients receiving panitumumab+FOLFOX4 and 2% receiving FOLFOX4 alone. There were no significant differences in quality of life between patients with grade 0-2 skin toxicity and those with grade 3+ skin toxicity. More patients receiving panitumumab+FOLFOX4 vs FOLFOX4 had early tumour shrinkage (p<.001). In patients with tumour symptoms at baseline, there were statistically significant improvements in quality of life in those with early tumour shrinkage versus those without early tumour shrinkage. Addition of panitumumab to FOLFOX4 in first-line therapy for metastatic colorectal cancer prolongs survival and has no negative effect on overall quality of life compared with FOLFOX4 alone. Specific quality of life assessments for skin toxicity should be included in study designs to better define the direct effect of these adverse events. NCT00364013

Bevacizumab plus paclitaxel versus placebo plus paclitaxel as first-line therapy for HER2-negative metastatic breast cancer (MERiDiAN): A double-blind placebo-controlled randomised phase III trial with prospective biomarker evaluation

Aim: MERiDiAN evaluated plasma vascular endothelial growth factor-A (pVEGF-A) prospectively as a predictive biomarker for bevacizumab efficacy in metastatic breast cancer (mBC). Methods: In this double-blind placebo-controlled randomised phase III trial, eligible patients had HER2-negative mBC previously untreated with chemotherapy. pVEGF-A was measured before randomisation to paclitaxel 90 mg/m2 on days 1, 8 and 15 with either placebo or bevacizumab 10 mg/kg on days 1 and 15, repeated every 4 weeks until disease progression, unacceptable toxicity or consent withdrawal. Stratification factors were baseline pVEGF-A, prior adjuvant chemotherapy, hormone receptor status and geographic region. Co-primary endpoints were investigator-assessed progression-free survival (PFS) in the intent-to-treat and pVEGF-Ahigh populations. Results: Of 481 patients randomised (242 placeboepaclitaxel; 239 bevacizumabepaclitaxel), 471 received study treatment. The stratified PFS hazard ratio was 0.68 (99% confidence interval, 0.51e0.91; log-rank p Z 0.0007) in the intent-to-treat population (median 8.8 months with placeboepaclitaxel versus 11.0 months with bevacizumabepaclitaxel) and 0.64 (96% con-fidence interval, 0.47e0.88; log-rank p Z 0.0038) in the pVEGF-Ahigh subgroup. The PFS treatment-by-VEGF-A interaction p value (secondary end-point) was 0.4619. Bevacizumab was associated with increased incidences of bleeding (all grades: 45% versus 27% with placebo), neutropenia (all grades: 39% versus 29%; grade 3: 25% versus 13%) and hypertension (all grades: 31% versus 13%; grade 3: 11% versus 4%). Conclusion: The significant PFS improvement with bevacizumab is consistent with previous placebo-controlled first-line trials in mBC. Results do not support using baseline pVEGF-A to identify patients benefitting most from bevacizumab. Clinical trials registration: ClinicalTrials.gov NCT01663727

Tumor lysis syndrome following trastuzumab and pertuzumab for metastatic breast cancer: a case report.

Tumor lysis syndrome is a rare and potentially fatal complication of oncologic treatments, especially in solid tumors. To the best of our knowledge, tumor lysis syndrome has never been reported after trastuzumab and pertuzumab combination therapy. Knowledge of risk factors and active prevention proceedings is of utmost importance to avoid fatal outcomes

Oral mucositis induced by anticancer treatments: physiopathology and treatments.

Oral mucositis is a frequent and devastating side effect of anticancer treatments. It impairs the patient's quality of life and also can be life threatening because severe infections and delayed or incomplete anticancer treatments may result. This problem has been largely overlooked and underestimated in the past. However, recently studies have been performed to precisely identify the epidemiology, cost, consequences, physiopathology, and treatments of oral mucositis. Clinical guidelines have recently been published to help the daily management of this frequent complication. In addition, some innovative new drugs, including palifermin, have been developed to prevent and treat this major side effect of cancer treatments. In this paper we summarize the recent developments of oral mucositis management

Clostridium tertium bacteremia: contamination or true pathogen? A report of two cases and a review of the literature

We observed two cases of Clostridium tertium bacteremia three months apart in the sterile unit of our department of hematology and oncology. One patient was being treated for first-relapse acute myeloblastic leukemia, while the second was receiving high-dose chemotherapy with hematopoietic stem cell support for non-Hodgkin lymphoma. At the time that C. tertium was identified, the first patient was completely asymptomatic, while the second was highly febrile. Both responded biologically and/or clinically to antibiotherapy. We discuss the epidemiology and pathology of C. tertium in the general and cancer patient population. (C) 2010 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved

Nodular regenerative hyperplasia : a deleterious consequence of chemotherapy for colorectal liver metastases?

AIMS: This report describes three patients suffering from nodular regenerative hyperplasia (NRH). METHODS: These patients have received six, 16 and 20 cycles of neoadjuvant 5-fluorouracil and oxaliplatin-based chemotherapy before planned extended hepatectomy. Two patients underwent uneventful portal vein embolization to hypertrophy the future remnant liver. RESULTS: At the end of chemotherapy, liver function tests deteriorated and portal hypertension appeared in two patients, including ascites, splenomegaly and oesophageal varices. Liver biopsy was performed through a percutaneous (two patients) or a transjugular approach (one patient) and allowed the diagnosis of NRH, which was considered to be a contraindication for major liver resection in all three patients, associated with extrahepatic disease progression in one patient. All patients died from neoplastic disease progression despite further chemotherapy at 6, 17 and 31 months following the diagnosis of NRH. One patient developed liver failure and ascites at the time of death. CONCLUSIONS: Physicians should be aware of the potential occurrence and therapeutic impact of NRH in patients suffering from CRLM and treated by neoadjuvant 5FU-oxaliplatin-based chemotherapy before major liver surgery