Docetaxel for the treatment of bladder cancer

Introduction: Docetaxel has had a significant impact on the management of urothelial carcinoma (UC). Multiple phase II trials have been conducted to evaluate the efficacy of docetaxel in the treatment of metastatic UC. Docetaxel is an accepted community standard for the therapy of platinum-treated patients with metastatic UC.

Areas covered: This review focuses on the data supporting a role for docetaxel in the therapy of advanced UC. It also explores the future development of docetaxel and describes the ongoing clinical trials in the treatment of UC.

Expert opinion: Docetaxel plays an important role as one of the standard agents used in the comparator arms of randomized trials evaluating new agents as salvage therapy for metastatic UC. Furthermore, biologic agents are being developed in chemo-biologic regimens using docetaxel as the platform. In the context of emerging novel agents such as T-cell checkpoint inhibitors, docetaxel may continue to play a role as a salvage therapy in select patients ineligible for immunotherapy or following checkpoint inhibitors.     

The analgesic effect of gabapentin and mexiletine after breast surgery for cancer

We investigated the analgesic efficacy of mexiletine and gabapentin on acute and chronic pain associated with cancer breast surgery in 75 patients. They were randomized to receive, in a double-blinded manner, mexiletine 600 mg/d, gabapentin 1200 mg/d, or placebo for 10 days. Anesthesia was standardized, and all patients had access to routine postoperative analgesics on demand. The visual analog scale score assessed pain at rest and after movement. Three months later, all patients were interviewed to identify intensity of chronic pain and analgesic requirements. Mexiletine and gabapentin reduced codeine consumed from the second to tenth day by 50% (P = 0.029; P = 0.018 and P = 0.035 for mexiletine versus control and gabapentin versus control comparisons, respectively). Total paracetamol consumption was also reduced during the same time (P = 0.0085; P = 0.007 and P = 0.011 for the mexiletine and gabapentin groups when compared with the control, respectively). Pain at rest and after movement was reduced by both drugs on the third postoperative day. Pain after movement also was reduced by gabapentin between the second and fifth postoperative day. Three months later, the incidence of chronic pain, its intensity, and need for analgesics were not affected by either treatment. However, burning pain was more frequent in the control group (P = 0.033). IMPLICATIONS: Patients undergoing breast surgery for cancer may develop chronic pain. We evaluated the effect of mexiletine and gabapentin on the acute and chronic pain after breast surgery for cancer. Both drugs reduced the postoperative analgesic requirements, and particularly, gabapentin reduced pain after movement. The overall incidence of chronic pain was unaffected except for burning pain.     

User fees impact access to healthcare for female children in rural Zambia

The World Bank and International Monetary Fund favor healthcare user fees. User fees offer revenue and may decrease inappropriate care. However, user fees may deter needed care, especially in vulnerable populations. A cross-sectional analysis of healthcare utilization in a large Zambian hospital was conducted for children 3-6 years of age during a 1-month observation period. Diagnoses and treatments were compared using paired t-tests. Chi-squared tests compared outpatient service use. The relative risk of admission was determined for each stratum. Logistic models were developed to evaluate the impact of age, gender, and the age-gender interaction on hospital admissions. Trends suggest female children may be less likely to present for care when user fees are imposed. However, treatment type, treatment number, and number of diagnoses did not differ between genders. The relative risk of admission was highest for males 5-6 years old. Neither age nor gender alone was a significant determinant of hospital admission. However, the age-gender interaction was significant with female admissions least likely when costs were incurred. We conclude that user fees appear to decrease differentially utilization of inpatient care for female children in rural Zambia.     

Phase 2 Trial of Gemcitabine,Cisplatin, plus Ipilimumab in Patients with Metastatic Urothelial Cancer and Impact of DNA Damage Response Gene Mutations on Outcomes

Background

Chemotherapy may exert immunomodulatory effects, thereby combining favorably with the immune checkpoint blockade. The pharmacodynamic effects of such combinations, and potential predictive biomarkers, remain unexplored.

Phase II study of fosaprepitant + 5HT3 receptor antagonist + dexamethasone in patients with germ cell tumors undergoing 5-day cisplatin-based chemotherapy: a Hoosier Cancer Research Network study

Purpose

A phase III study adding aprepitant to a 5HT3 receptor antagonist (5HT3-RA) plus dexamethasone in germ cell tumor (GCT) patients treated with 5-day cisplatin combination chemotherapy demonstrated a significant improvement in complete response (CR) (J Clin Onc 30:3998-4003, 2012). Fosaprepitant has demonstrated non-inferiority compared to aprepitant in single-day cisplatin chemotherapy and is approved as a single-dose alternative. This single-arm phase II study is the first clinical trial evaluating fosaprepitant in patients receiving multi-day cisplatin regimen.

Methods

GCT patients receiving a 5-day cisplatin combination chemotherapy were enrolled. Fosaprepitant 150 mg was given IV on days 3 and 5. A 5HT3-RA days 1–5 (days 1, 3, and 5, if palonosetron) plus dexamethasone 20 mg days 1 and 2 and 4 mg po bid days 6, 7, and 8 was administered. Rescue antiemetics were allowed. The primary objective was to determine the CR rate—no emetic episodes or use of rescue medications. Accrual of 64 patients was planned with expected CR?>?27 %.

Results

Sixty-five patients were enrolled of whom 54 were eligible for analysis. Median age was 33. Fifty-one patients received bleomycin, etoposide, and cisplatin (BEP) chemotherapy. CR was observed in 13 (24.1 %) patients (95 % Agresti-Coull binomial C.I. 14.5 %, 37.1 %).

Conclusion

The data in this phase II study, in contrast to our prior phase III study, appears to indicate a lower CR rate with the substitution of fosaprepitant for aprepitant. It is unknown whether the substitution of fosaprepitant for aprepitant provides the same benefit in multi-day cisplatin that was achieved with single-day cisplatin. Trial registration Clinical trial information NCT01736917

     

Plasmapheresis in asparaginase-induced hypertriglyceridemia

BACKGROUND: Asparaginase is an essential component of the chemotherapy regimens during the induction and intensification phases for acute lymphoblastic leukemia and lymphoblastic lymphoma. The administration of asparaginase can cause elevation of the triglyceride levels. CASE REPORT: This study reports the case of an adult patient presenting with acute pancreatitis secondary to severe hypertriglyceridemia after asparaginase treatment during the consolidation phase of lymphoblastic lymphoma. This condition was successfully treated with plasmapheresis. CONCLUSIONS: Our case demonstrates that plasmapheresis in severe cases of hypertriglyceridemia offers a safe and efficient treatment option for symptomatic patients.