Molecularly targeted therapy: toxicity and quality of life considerations in advanced colorectal cancer.

Colorectal cancer (CRC) is the third most common malignancy and cause of death from cancer among adults worldwide. In recent years, the use of 5-fluorouracil-based regimens in combination with molecularly targeted agents has greatly expanded treatment options for patients with metastatic disease. With a more capillary use of this new class of agents comes the recognition of diverse adverse events related to disturbance of critical biological pathways involved in physiological functions. Proactive management and prevention of adverse events, with a focus on the necessary compromise between adverse events and tumor control, are often effective and allows for uninterrupted, full-dose therapy with targeted agents. Quality of life does not appear deteriorated, rather improved due to efficacy in prolonging wellness.

Effectiveness and safety of oxaliplatin compared to cisplatin for advanced, unresectable gastric cancer: a systematic review and meta-analysis.

BACKGROUND: Cisplatin has been largely used in the treatment of advanced, unresectable gastric cancer, mainly in combinations with fluoropyrimidines and anthracyclines. Oxaliplatin has been shown to be at least as effective as cisplatin for this disease, but with less toxicity and a better tolerability profile, especially for older patients. We performed a systematic review of the literature to address and quantify differences in the efficacy and the safety between oxaliplatin and cisplatin for the treatment of this disease. METHODS: The literature was searched for randomized controlled trials (RCTs) comparing oxaliplatin to cisplatin. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to analyze dichotomous variables. Hazard ratios (HRs) for progression and death were combined with an inverse variance method based on logarithmic conversion. A fixed effect model and Mantel-Haenszel's (M-H) method were used. Heterogeneity was tested with the Q test and the I (2) value. Sensitivity analyses were performed. RESULTS: Three RCTs were identified, involving a total of 1294 patients. Oxaliplatin significantly improved progression-free survival (HR = 0.88, p = 0.02) and overall survival (HR = 0.88, p = 0.04). Moreover, it was associated with less neutropenia (OR = 0.53, p < 0.01) and fewer thromboembolic events (OR = 0.42, p < 0.01), but it was also associated with increased neurotoxicity (OR = 6.91, p < 0.01). CONCLUSIONS: Our results support the existence of a small but significant survival benefit of oxaliplatin over cisplatin. Oxaliplatin is associated with less toxicity and better tolerability, especially in older patients and when used in two-drug, bi-weekly regimens.

Congestive heart failure during imatinib mesylate treatment.

Imatinib mesylate (IM) is a very important drug in the treatment of gastrointestinal stromal tumors (GISTs) and chronic myeloid leukaemia (CML). In large clinical trials conducted until now it demonstrated a good cardiac safety profile. However during the last years many reports indicated a possible IM-induced cardiotoxicity. Here we report a case of a patient with a GIST who developed a severe and irreversible cardiac failure during IM treatment. Interestingly, she suffered from chronic renal failure, a condition that does not contraindicate treatment. Our opinion is that IM-induced cardiotoxicity could be facilitated by the presence of relevant comorbidities such as pre-existing cardiovascular disease or renal failure, commonly present in daily practice but excluded from clinical trials. Phase IV studies are needed to address the question of the real incidence of IM-induced cardiotoxicity in the general population.

Persistent thrombocytopenia during melanoma treatment with fotemustine.

Haematological toxicity characterized by delayed and reversible neutropenia and/or thrombocytopenia is an adverse effect observed in 40% of patients receiving fotemustine. We report the case of a 66-year-old man with metastatic malignant melanoma treated with fotemustine as monotherapy. A severe persistent and prolonged thrombocytopenia occurred, so that chemotherapy was discontinued. Bone marrow involvement was excluded. The physician should be aware of this prolonged thrombocytopenia secondary to fotemustine, so that it may be recognized early and not attributed erroneously to tumour evolution. This observation could be substantial for the design of combination regimens with fotemustine and other myelotoxic drugs in pretreated melanoma patients.

"Misura" project: a retrospective survey on the use of 5fluorouracil in the treatment of colorectal cancer in 24 Italian clinical centers.

The "Misura" project is a retrospective survey, with the aim to evaluate how 5FU is used in the treatment of colorectal cancer in clinical practice in Italian oncology departments. Twenty-four centers participated. Patients seen in the second half of 1998 with colorectal cancer and treated with 5FU were analyzed. Observed patients were 664, 45.9% of patients presented metastatic disease. Biochemical modulation with folinic acid and bolus 5FU was the most used schedule (59%). The De Gramont (LV 5FU2) regimen, alone or with other cytotoxic drugs, was the second most chosen schedule (14%). The most frequent side effect observed was gastrointestinal toxicity. No hematological toxicity was demonstrated in 68.8% of patients. Cutaneous toxicity occurred in 21.1% of patients. 5FU is widely used independently by the stage of disease. In palliative treatment a variety of schedules were administered by the Italian centers, lacking a standard therapy. There are very few surveys investigating oncology clinical practice. A larger survey on this issue is auspicable.