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.

Prognostic significance of the neutrophil/lymphocyte ratio in patients undergoing treatment with nivolumab for recurrent non-small-cell lung cancer.

AIM: We investigated the prognostic potential of pretherapy measurement of the neutrophil/lymphocyte ratio (NLR) in patients (n = 56) with non-small-cell lung cancer deemed suitable for treatment with nivolumab. MATERIALS & METHODS: This was a multicenter, noninterventional, retrospective data analysis, involving five oncology centers. RESULTS: Patients with prenivolumab NLR values of <5 and ≥5 had respective median overall survival (OS) values of 14.5 and 7.02 months (p = 0.0026). Patients with ≤2 and >2 metastatic sites had median OS values of 11.4 and 6.1 months, respectively (p = 0.0174). A Cox multiple regression model revealed baseline NLR ≥5 as the only variable significantly associated with decreased OS (p < 0.0447). CONCLUSION: Pretreatment elevated NLR values are associated with poor outcomes in patients with recurrent metastatic non-small-cell lung cancer treated with nivolumab.

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.

Recent advances in the medical treatment of breast cancer.

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.

Rituximab Maintenance for a Maximum of 5 Years After Single-Agent Rituximab Induction in Follicular Lymphoma: Results of the Randomized Controlled Phase III Trial SAKK 35/03.

PURPOSE: Rituximab maintenance therapy has been shown to improve progression-free survival in patients with follicular lymphoma; however, the optimal duration of maintenance treatment remains unknown. PATIENTS AND METHODS: Two hundred seventy patients with untreated, relapsed, stable, or chemotherapy-resistant follicular lymphoma were treated with four doses of rituximab monotherapy in weekly intervals (375 mg/m(2)). Patients achieving at least a partial response were randomly assigned to receive maintenance therapy with one infusion of rituximab every 2 months, either on a short-term schedule (four administrations) or a long-term schedule (maximum of 5 years or until disease progression or unacceptable toxicity). The primary end point was event-free survival (EFS). Progression-free survival, overall survival (OS), and toxicity were secondary end points. Comparisons between the two arms were performed using the log-rank test for survival end points. RESULTS: One hundred sixty-five patients were randomly assigned to the short-term (n = 82) or long-term (n = 83) maintenance arms. Because of the low event rate, the final analysis was performed after 95 events had occurred, which was before the targeted event number of 99 had been reached. At a median follow-up period of 6.4 years, the median EFS was 3.4 years (95% CI, 2.1 to 5.3) in the short-term arm and 5.3 years (95% CI, 3.5 to not available) in the long-term arm (P = .14). Patients in the long-term arm experienced more adverse effects than did those in the short-term arm, with 76% v 50% of patients with at least one adverse event (P < .001), five versus one patient with grade 3 and 4 infections, and three versus zero patients discontinuing treatment because of unacceptable toxicity, respectively. There was no difference in OS between the two groups. CONCLUSION: Long-term rituximab maintenance therapy does not improve EFS, which was the primary end point of this trial, or OS, and was associated with increased toxicity.

Bone targeted therapies in early breast cancer.

OPINION STATEMENT: Bisphosphonates have emerged as an important tool in the supportive care of women with early breast cancer. Whereas traditionally, these drugs have been part of the treatment of osseous metastasis, the key role of bisphosphonates in preserving bone health in patients with early breast cancer cannot be overemphasised. Currently the most established use of bisphosphonates in early breast cancer patients is in women receiving hormonal blockade, mostly aromatase inhibitors (AI), with concomitant osteopenia. To that end, it is recommended that every woman undergo a Dual Energy X-Ray absorptiometry (DEXA) scan before commencement of an AI and annually during the treatment duration. In addition, unless contraindicated, all women should receive calcium and Vitamin D supplementation. The use of bisphosphonates as part of the adjuvant therapy strategy, regardless of baseline bone density condition, has produced thought-provoking results, although this is not yet considered standard clinical practise.

Malignant pleural mesothelioma: medical treatment update.

Malignant pleural mesothelioma (MPM) is a disease usually unaffected by current therapeutic strategies, but for the majority of patients, the use of systemic chemotherapeutic drugs remains the only therapeutic option available. During the past 15-20 years, many phase II and a few phase III clinical trials have studied a large variety of drugs such as anthracyclines, alkylating agents, platinum compounds, taxanes, vinka alkaloids, and antifolates as single agents and in combination, with the aim to increase responses and survival. The combination of pemetrexed and cisplatin tested in the largest phase III randomized trial of malignant pleural mesothelioma ever conducted has become the current standard of care. New targeted therapeutic approaches with a variety of anti-growth factor drugs are currently undergoing investigation worldwide.

Asbestos and mesothelioma in South Africa.

Asbestos has been used by man since 4000 before the Christian era (BCE) in many different parts of the world and for a wide range of functions. Blue asbestos (crocidolite) was first discovered in South Africa in 1805 and within a few years was being mined there extensively. Mining reached its peak in 1977 with >380,000 tons being exported and 20,000 miners employed in the industry. South Africa also has large deposits of white asbestos (chrysotile) and brown asbestos (amosite) both of which have been mined extensively. At the turn of the 20th century, it was noted that those working with asbestos suffered lung disease and in 1960, the link between asbestosis and mesothelioma was established in the Kimberley area of South Africa. Further studies in the 1970s and 1980s showed an alarming incidence of mesothelioma based on pathology reports. The majority of the reported mesothelioma cases result from exposure to asbestos in its many uses in secondary industry although incidence of the condition among miners is also significant. A high proportion of mesothelioma in patients in South Africa is attributed to environmental origin with a high incidence of women and children affected.

Primary osteosarcoma of the breast: a case report.

We report a rare case of primary osteosarcoma of the breast in a postmenopausal patient without any association to either trauma or an underlying tumor. Clinical, radiographic, and histologic illustrations as well as a review of the literature are presented.

Phase II study of pegylated liposomal doxorubicin in patients with metastatic malignant melanoma failing standard chemotherapy treatment.

Fourteen patients with metastatic malignant melanoma that had failed to respond to standard dacarbazine-based chemotherapy treatment were entered into a phase II study of pegylated liposomal doxorubicin (Caelyx) given as a single intravenous injection at a dose of 50 mg/m(2) at 28 day intervals. No objective responses were documented. Treatment was well tolerated. We conclude that pegylated liposomal doxorubicin does not demonstrate sufficient activity in metastatic melanoma to warrant further investigation in this setting.