Cancer drugs: Highlighting the molecular mechanisms of cardiotoxicity

The treatment options for patients with cancer have increased rapidly in the last decade with the introduction of newer chemotherapy drugs, targeted agents and monoclonal antibodies. Most of these drugs are aimed at interrupting proliferative signalling, with consequent apoptosis of cancer cells. Because most of the new drugs are multi-targeted, there is a likelihood of so called “off target” effects, where other kinases which are not the primary targets of the drug, are also inhibited. This has led to unforeseen toxicities and, in this commentary, we will focus on the molecular mechanisms underlying cardiotoxicities as a result of cancer therapies. However, cardiotoxicity is not a new concern as the older generation chemotherapies, like anthracyclines, are known to commonly cause irreversible cardiomyopathy, mostly as a result of induced DNA damage and oxidative stress. Over the years, clinicians have adopted some methods of diminishing the incidence of this side-effect and therefore improving patient safety. Trying to decipher the complicated pathways underlying cardiotoxicity helps the scientifi c community to design new drugs that are tumoricidal, whilst sparing normal tissue and as such limiting unwanted side-effects. This has become ever so important, as oncologists cure more patients of cancer, and some previously incurable cancers are increasingly being converted into chronic illnesses. A relationship between the cardiologist and the oncologist has become mandatory to ensure close monitoring of such patients and offering appropriate management, should cardiotoxicities arise

Guidelines for CPD accreditation of the South African Society of Medical Oncology

There do not appear to be guidelines in use for accreditation of continuing professional development (CPD) activities in South Africa, or indeed in many other parts of the world. The South African Society of Medical Oncology (SASMO) has adopted the guidelines below, based in part on the guidelines of the Canadian Medical Association for the interaction between industry and doctors

Recent advances in the medical treatment of breast cancer [version 1; referees: 2 approved]

Over the past few decades, the systemic therapy of breast cancer (early and advanced) has changed considerably. For the past 40–50 years, and since the discovery and further therapeutic use of tamoxifen, a selective estrogen receptor modulator, breast cancer treatment has become the model for the development and success of tailored medical treatment. Much still needs to be done in improving outcomes for all patients with breast cancer, and especially for those who have advanced breast cancer, a challenging area for medical oncologists. Ongoing international clinical trials are currently evaluating new therapeutic approaches and identifying specific biological subsets that could determine a patient’s ability to respond to particular chemotherapeutic drugs

Ipilimumab in Pretreated Patients With Advanced Malignant Melanoma: Results of the South African Expanded-Access Program

Purpose: The primary objective of this study was to evaluate 1- and 2-year survival rates and durable remissions in pretreated patients with advanced (unresectable or metastatic) malignant melanoma treated with ipilimumab in a South African expanded-access program (SA-EAP). Patients and Methods: This multicenter, retrospective study obtained data from pretreated patients with advanced malignant melanoma who were eligible for the ipilimumab SA-EAP. Ipilimumab was administered at a dose of 3 mg/kg intravenously every 3 weeks for four cycles to adults with advanced melanoma for whom at least one line of treatment for metastatic disease had failed. Data from the medical records of 108 patients treated within the SA-EAP were collected and statistically analyzed to determine overall (OS) and progression-free survival (PFS) at 1 and 2 years. Results: In the population of 108 patients, a median OS of 8.98 months (95% CI, 7.47 to 10.79 months) was observed. One-year OS was 36% (95% CI, 26% to 45%), and 2-year survival was observed as 20% (95% CI, 12% to 27%). The median survival without progression (ie, PFS) was 3.44 months (95% CI, 2.98 to 4.16 months), and 1- and 2-year PFS were 22% (95% CI, 14% to 29%) and 14% (95% CI, 8% to 21%), respectively. The longest recorded survival was 3.4 years. No independent prognostic variables were identified to predict for OS by multivariate Cox proportional hazards model. Conclusion: In this multicenter South African setting, ipilimumab at a dose of 3 mg/kg was an effective treatment with long-term OS in a subset of patients with pretreated advanced malignant melanoma

Prolonged rituximab maintenance in follicular lymphoma patients: long-term results of the SAKK 35/03 randomized trial.

The Swiss Group for Clinical Cancer Research (SAKK) conducted the SAKK 35/03 randomized trial (NCT00227695) to investigate different rituximab monotherapy schedules in patients with follicular lymphoma (FL). Here, we report their long-term treatment outcome. Two-hundred and seventy FL patients were treated with 4 weekly doses of rituximab monotherapy (375 mg/m2); 165 of them, achieving at least a partial response, were randomly assigned to maintenance rituximab (375 mg/m2 every 2 months) on a short-term (4 administrations; n = 82) or a long-term (up to a maximum of 5 years; n = 83) schedule. The primary end point was event-free survival (EFS). At a median follow-up period of 10 years, median EFS was 3.4 years (95% confidence interval [CI], 2.1-5.5) in the short-term arm and 5.3 years (95% CI, 3.5-7.5) in the long-term arm. Using the prespecified log-rank test, this difference is not statistically significant (P = .39). There also was not a statistically significant difference in progression-free survival or overall survival (OS). Median OS was 11.0 years (95% CI, 11.0-NA) in the short-term arm and was not reached in the long-term arm (P = .80). The incidence of second cancers was similar in the 2 arms (9 patients after short-term maintenance and 10 patients after long-term maintenance). No major late toxicities emerged. No significant benefit of prolonged maintenance became evident with longer follow-up. Notably, in symptomatic patients in need of immediate treatment, the 10-year OS rate was 83% (95% CI, 73-89%). These findings indicate that single-agent rituximab may be a valid first-line option for symptomatic patients with advanced FL