cabazitaxel and Fatigue

Despite a growing number of treatment options, metastatic castrate resistant prostate cancer remains almost universally fatal. Dose individualization ensures patients receive the maximal benefit from each line of treatment potentially leading to improved outcomes, a reduction in quality of life impairment and minimization of premature cessation for avoidable toxicity. Herein, we review drug-specific issues that may be associated with unexpected or unrecognized variations in drug systemic exposure despite the use of protocol doses. In particular, we discuss the potential for under-exposure of docetaxel and cabazitaxel; over-exposure of enzalutamide; and varied absorption of abiraterone acetate.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cognition Disorders; Docetaxel; Dose-Response Relationship, Drug; Fatigue; Humans; Male; Precision Medicine; Prostatic Neoplasms, Castration-Resistant; Taxoids

Cabazitaxel, a novel taxane, was approved in June 2010 by the U.S. Food and Drug Administration for treatment of metastatic castrate-resistant prostate cancer (mCRPC) in men previously treated with docetaxel. In TROPIC (N = 755), an open-label, randomized, phase III trial, cabazitaxel (plus prednisone) was associated with improvement in median overall survival compared with mitoxantrone plus prednisone (15.1 versus 12.7 months, p < 0.0001) in patients with mCRPC who had progressed following docetaxel-based regimens. That corresponds to a 30% relative reduction in risk of death compared with the mitoxantrone regimen. In addition, significant benefit existed in median progression-free survival with cabazitaxel versus the mitoxantrone regimen (2.8 versus 1.4 months, p < 0.0001). Most common adverse events (AEs) associated with cabazitaxel were hematologic; the rates (all grade) of neutropenia, leukopenia, and anemia were greater than 90%. Diarrhea, fatigue, asthenia, and back pain were the most common grade 3 or higher nonhematologic AEs. Because expected AEs from cabazitaxel therapy can delay or even interrupt treatment, oncology nurses need to be aware of those risks and their management. This article reviews the vital role of nurses in identifying patients at high risk for AEs associated with cabazitaxel therapy and reviews strategies for prevention and management of symptoms.

Topics: Antineoplastic Agents; Clinical Trials, Phase III as Topic; Fatigue; Gastrointestinal Diseases; Humans; Infusions, Intravenous; Male; Neutropenia; Nursing Assessment; Oncology Nursing; Orchiectomy; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Risk Assessment; Taxoids

Cabazitaxel, a semisynthetic microtubule inhibitor, has shown antitumour activity in models resistant to paclitaxel and docetaxel, and it has been approved for the treatment of docetaxel-resistant prostate cancer. We investigated its activity in patients with advanced non-small-cell lung cancer (NSCLC) progressing under or after docetaxel-based regimens.. Patients with locally advanced unresectable or metastatic NSCLC, with an Eastern Cooperative Oncology Group performance status of 0-2, were enrolled; patients had to have received up to two prior chemotherapy regimens for the treatment of advanced disease, including one docetaxel-containing regimen. Treatment consisted of cabazitaxel (25 mg m(-2) intravenously, every 21 days) until disease progression. The primary end point was the overall response rate.. Among the 46 evaluable patients, 28.3% had squamous cell carcinoma and 54.3% had adenocarcinoma. Eight (17.4%) patients had received one and 38 (82.6%) two prior chemotherapy regimens. Treatment compliance was 95%; 26 (16%) cycles were delayed because of toxicity, (n=13) and dose reduction was required in 6 (13%) patients because of haematologic toxicity. Six (13%) patients achieved a partial response and 17 (37.0%) stable disease. The median progression-free survival and overall survival were 2.1 (95% confidence interval (CI): 1.0-3.2) and 7.4 (95% CI: 5.2-9.6) months, respectively. Grade 4 adverse events included neutropenia (n=8; 17%), febrile neutropenia (n=6; 13%) and thrombocytopenia (n=3; 6.5%). There was one treatment-related death.. Cabazitaxel exhibits activity in NSCLC patients pre-treated with docetaxel-based chemotherapy with a substantial but manageable toxicity profile. The drug merits further evaluation in this indication.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Large Cell; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Disease-Free Survival; Docetaxel; Drug Resistance, Neoplasm; Drug Substitution; Dyspnea; Fatigue; Female; Gastrointestinal Diseases; Greece; Hematologic Diseases; Humans; Kaplan-Meier Estimate; Lung Neoplasms; Male; Middle Aged; Taxoids; Treatment Outcome

To report the efficacy and safety of using cabazitaxel plus prednisolone chemotherapy to treat Korean patients with metastatic castration-resistant prostate cancer (mCRPC) following docetaxel therapy.. This cohort study enrolled 26 mCRPC patients. Treatment consisted of 25 mg/m(2) cabazitaxel that was intravenously administered every 3 weeks, in addition to twice-daily 5 mg prednisolone.. The median patient age was 67 years (range = 53-82), median Eastern Cooperative Oncology Group performance status was 1 (range = 0-2), Gleason score was ≥ 8 in 25 patients (96 %), and median serum prostate-specific antigen (PSA) was 95.3 ng/mL (interquartile range = 9.1-297.7). A total of 180 treatment cycles were administered, and a median of five cycles were administered per patient (range = 1-23). A PSA response was observed in 32 % of evaluable patients. Tumor response was evaluated in eight patients, and three and four patients achieved partial response and stable disease, respectively. Over a median follow-up duration of 23.4 months (95 % CI 11.1-35.6), median time to treatment failure was 4.2 months (95 % CI 1.8-6.6) and median time to progression was 8.5 months (95 % CI 3.0-13.1). Median overall survival was 16.5 months (95 % CI 12.1-20.9). Grade 3 or worse febrile neutropenia developed in eight patients (31 %) and neutropenic infection in four patients (15 %).. Cabazitaxel plus prednisolone chemotherapy can be used to treat Korean mCRPC patients. Prophylactic growth factor support should be considered for patients at high risk of neutropenic fever or infection.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anemia; Antineoplastic Combined Chemotherapy Protocols; Asian People; Cohort Studies; Compassionate Use Trials; Diarrhea; Drug Administration Schedule; Fatigue; Humans; Infusions, Intravenous; Kaplan-Meier Estimate; Male; Middle Aged; Neoplasm Grading; Neoplasm Metastasis; Neutropenia; Prednisolone; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Republic of Korea; Taxoids; Treatment Outcome