cabazitaxel and Pain

Cabazitaxel significantly improves overall survival (OS) versus mitoxantrone in patients with metastatic castration-resistant prostate cancer after docetaxel failure. We examined patient survival at 2 years and tumour-related pain with cabazitaxel versus mitoxantrone.. Updated TROPIC data (cut-off 10 March 2010) were used to compare 2-year survival between treatment groups and assess patient demographics and disease characteristics. Factors prognostic for survival ≥2 years were assessed. Pain and Eastern Cooperative Oncology Group performance status were evaluated in the overall patient population.. Median follow-up was 25.5 months. After 2 years, more patients remained alive following cabazitaxel than mitoxantrone [odds ratio 2.11; 95% confidence interval (CI) 1.33-3.33]. Treatment with cabazitaxel was prognostic for survival ≥2 years. Demographics/baseline characteristics were balanced between treatment arms irrespective of survival. Pain at baseline and pain response were comparable between treatment groups. Average daily pain performance index was lower for cabazitaxel versus mitoxantrone (all cycles; 95% CI -0.27 to -0.01; P = 0.035) and analgesic scores were similar. Grade ≥3 peripheral neuropathies were uncommon and comparable between treatment groups.. Cabazitaxel prolongs OS at 2 years versus mitoxantrone and has low rates of peripheral neuropathy. Palliation benefits of cabazitaxel were comparable to those of mitoxantrone. The study was registered with www.ClinicalTrials.gov (NCT00417079).

Topics: Aged; Aged, 80 and over; Analgesics; Antineoplastic Agents; Docetaxel; Humans; Male; Middle Aged; Mitoxantrone; Neoplasm Metastasis; Pain; Pain Measurement; Palliative Care; Peripheral Nervous System Diseases; Prostatic Neoplasms, Castration-Resistant; Quality of Life; Survival; Survival Rate; Taxoids; Treatment Outcome

Several prognostic models for overall survival (OS) have been developed and validated in men with metastatic castration-resistant prostate cancer (mCRPC) who receive first-line chemotherapy. We sought to develop and validate a prognostic model to predict OS in men who had progressed after first-line chemotherapy and were selected to receive second-line chemotherapy.. Data from a phase III trial in men with mCRPC who had developed progressive disease after first-line chemotherapy (TROPIC trial) were used. The TROPIC was randomly split into training (n = 507) and testing (n = 248) sets. Another dataset consisting of 488 men previously treated with docetaxel (SPARC trial) was used for external validation. Adaptive least absolute shrinkage and selection operator selected nine prognostic factors of OS. A prognostic score was computed from the regression coefficients. The model was assessed on the testing and validation sets for its predictive accuracy using the time-dependent area under the curve (tAUC).. The nine prognostic variables in the final model were Eastern Cooperative Oncology Group performance status, time since last docetaxel use, measurable disease, presence of visceral disease, pain, duration of hormonal use, hemoglobin, prostate specific antigen, and alkaline phosphatase. The tAUCs for this model were 0.73 (95% confidence interval [CI] = 0.72 to 0.74) and 0.70 (95% CI = 0.68 to 0.72) for the testing and validation sets, respectively.. A prognostic model of OS in the postdocetaxel, second-line chemotherapy, mCRPC setting was developed and externally validated. This model incorporates novel prognostic factors and can be used to provide predicted probabilities for individual patients and to select patients to participate in clinical trials on the basis of their prognosis. Prospective validation is needed.

Topics: Aged; Alkaline Phosphatase; Antineoplastic Combined Chemotherapy Protocols; Area Under Curve; Biomarkers, Tumor; Docetaxel; Drug Administration Schedule; Hemoglobins; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Mitoxantrone; Models, Statistical; Multivariate Analysis; Nomograms; Organoplatinum Compounds; Pain; Predictive Value of Tests; Prednisone; Prognosis; Proportional Hazards Models; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Sensitivity and Specificity; Taxoids; Treatment Outcome

This prospective study collected quality of life (QoL) and pain data during cabazitaxel treatment in patients with advanced metastatic or castration-resistant prostate cancer (mCRPC).. Functional Assessment of Cancer Therapy-Prostate (QoL) and Brief Pain Inventory-Short Form (pain) questionnaires were collected over 6 months.. In 61 patients with mCRPC (median age, 72 years) from 22 centers, metastatic sites were bones (97%), lymph nodes (36%), and visceral (20%); 25% received cabazitaxel in the second line, 29% in the third line, and 46% in the fourth line or beyond. All had been previously treated with docetaxel, except one with paclitaxel, and 75% also with abiraterone, enzalutamide, or both. The median cabazitaxel duration was 3.4 months. Forty-nine patients were evaluable for QoL and 44 for pain. QoL was improved in 37%, maintained in 35%, and deteriorated in 37%. In 27%, pain decreased ≥ 1 level and remained stable in 52%. A total of 34% lowered analgesic drug level. Prostate-specific antigen response ≥ 50% was observed in 11 (32.6%) patients, of whom 7 improved QoL and 1 was stable. At 6 months, 83.6% survived (95% confidence interval, 71.7%-90.8%). A total of 46% had ≥ 1 grade ≥ 3 adverse events, mainly anemia and neutropenia.. Although cabazitaxel was given as the third line and beyond for three-quarters of patients, over one-third had improved QoL and/or decreased pain during treatment.

Topics: Aged; Humans; Male; Pain; Prospective Studies; Prostatic Neoplasms, Castration-Resistant; Quality of Life; Taxoids

To describe the patterns of second-line treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) after docetaxel treatment in a Spanish population, to identify the factors associated with those patterns, and to compare the efficacy and safety of the treatments most frequently administered.. Observational, prospective study conducted in patients with histologically or cytologically confirmed prostate adenocarcinoma; documented metastatic castration-resistant disease; progression after first-line, docetaxel-based chemotherapy with or without other agents.. Of the 150 patients recruited into the study, 100 patients were prescribed abiraterone acetate plus prednisone (AAP), 44 patients received cabazitaxel plus prednisone (CP), and 6 patients received other treatments. Age (odds ratio [OR] 1.06, 95% [confidence interval] CI 1.01 to 1.11) and not elevated lactate dehydrogenase (LDH) levels (OR 0.33, 95% CI 0.14 to 0.76) were independently associated with the administration of AAP. Treatment with AAP was associated with significantly longer clinical/radiographic progression-free survival (hazard ratio [HR] 0.57, 95% CI 0.38 to 0.85) and overall survival (OS; HR 0.40, 95% CI 0.21 to 0.76) compared to CP, while no significant differences between the treatments were found regarding biochemical progression-free survival (PFS; HR 0.78 [95% CI 0.49 to 1.24]). However, in a post-hoc Cox regression analysis adjusted for potential confounders there were not differences between AAP and CP in any of the time-to-event outcomes, including overall survival. We observed no new safety signals related to either regimen.. Second-line AAP for patients with mCRPC is the most common treatment strategy after progression with a docetaxel-based regimen. When controlling for potential confounders, patients receiving this treatment showed no differences in PFS and OS in comparison to those receiving CP, although these latter results should be confirmed in randomized controlled trials.

Topics: Abiraterone Acetate; Adenocarcinoma; Age Factors; Aged; Aged, 80 and over; Anemia; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Asthenia; Docetaxel; Humans; Kaplan-Meier Estimate; L-Lactate Dehydrogenase; Male; Middle Aged; Multivariate Analysis; Pain; Prednisone; Progression-Free Survival; Proportional Hazards Models; Prospective Studies; Prostatic Neoplasms, Castration-Resistant; Spain; Taxoids; Treatment Outcome

The aim of this study was to develop a novel cabazitaxel bone targeted nanoparticle (NP) system for improved drug delivery to the bone microenvironment.. Nanoparticles were developed using poly(D,L-lactic-co-glycolic acid) and cabazitaxel as the core with amino-bisphosphonate surface conjugation. Optimization of nanoparticle physiochemical properties, in vitro evaluation in prostate cancer cell lines and in vivo testing in an intraosseous model of metastatic prostate cancer was performed.. This bone targeted cabazitaxel nanocarrier system showed significant reduction in tumor burden, while at the same time maintaining bone structure integrity and reducing pain in the mouse tumor limb.. This bone microenvironment targeted nanoparticle system and clinically relevant approach of evaluation represents a promising advancement for treating bone metastatic cancer.

Topics: Animals; Antineoplastic Agents; Bone and Bones; Bone Neoplasms; Cell Line, Tumor; Cell Survival; Diphosphonates; Drug Carriers; Drug Liberation; Humans; Lactic Acid; Male; Mice; Mice, Nude; Nanoparticles; Pain; Particle Size; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Prostatic Neoplasms; Surface Properties; Taxoids; Xenograft Model Antitumor Assays

To examine health-related quality of life (QoL) in men with metastatic castration-resistant prostate cancer (mCRPC) on cabazitaxel.. Men with mCRPC receiving cabazitaxel (25 mg/m², every 3 weeks) and 10 mg/day oral prednis(ol)one were enrolled (2011-2014) in the non-interventional prospective 'QoLiTime' study. Primary outcome was change in QoL (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire 30-item) with respect to prostate-specific antigen (PSA) response after four cycles of cabazitaxel. Secondary outcomes included occurrence of adverse events (AEs).. Of 527 men, 348 received four cycles of cabazitaxel and 266 had the necessary PSA level measurements. After four cycles, 92 (34.6%) men had a PSA level decrease ≥50% (responders). QoL remained stable throughout the study (P = 0.62). Change in QoL did not differ between responders and non-responders (P = 0.69). Change in PSA level and global health status between baseline and four cycles showed an inversely proportional relationship (correlation coefficient -0.14; 95% confidence interval -0.26 to -0.01; P = 0.03), with increasing PSA level corresponding to lower health status. Responders showed no change in physical functioning vs baseline (-1.75, P = 0.12); non-responders showed a reduction vs baseline (-7.00, P < 0.001) and responders (P = 0.05). Responders showed an improvement in pain vs baseline (-7.61, P = 0.05) and vs non-responders (P = 0.01). AEs occurred in 292 patients (55.4%), most commonly anaemia (16.5%), fatigue (12.3%) and diarrhoea (11.8%). Neutropenia and febrile neutropenia were reported in 3.8% and 3.6% of patients, respectively.. Prostate-specific antigen level response was associated with stable physical functioning and improvement in pain. Symptom increases were seen in areas typical of chemotoxicity, but QoL was maintained.

Topics: Adult; Aged; Aged, 80 and over; Humans; Male; Middle Aged; Pain; Pain Management; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Quality of Life; Taxoids