Impact of Body Mass Index on the Incidence of Bortezomib-induced Peripheral Neuropathy in Patients With Newly Diagnosed Multiple Myeloma.

BACKGROUND: Peripheral neuropathy is one of the most common dose-limiting toxicities associated with bortezomib; it can lead to dose reductions or therapy discontinuation. Obesity has been identified as being a risk factor for the development of peripheral neuropathy with other neurotoxic anticancer agents. We aimed to evaluate the impact of obesity on the incidence and severity of bortezomib-induced peripheral neuropathy. PATIENTS AND METHODS: This is a retrospective, single-center study of patients treated with subcutaneous bortezomib between January 1, 2012 and June 1, 2017. Eligible patients received at least 1 full cycle of subcutaneous bortezomib and had previously untreated, newly diagnosed multiple myeloma. Patients who received intravenous bortezomib or concomitant thalidomide were excluded. Patients were divided into 3 groups based on their body mass index (BMI): normal/underweight (BMI < 25), overweight (BMI = 25-29.9), and obese (BMI ≥ 30). RESULTS: A total of 143 patients fitting the inclusion criteria were identified. Patients across the 3 groups received bortezomib at similar doses and schedules (weekly vs. biweekly). Obese patients had an increased incidence in developing bortezomib-induced peripheral neuropathy (56.4%) compared with normal/underweight (17.3%) and overweight patients (26.9%). Further analysis showed that, compared with normal/underweight and overweight patients, obesity was not found to be associated with an increased risk of grade 3 to 4 bortezomib-induced peripheral neuropathy (P = .451). CONCLUSION: Obese patients were found to be at higher risk for the development of bortezomib-induced peripheral neuropathy compared with non-obese patients.

Neutropenia-Associated Outcomes in Patients With Breast Cancer Receiving Myelosuppressive Chemotherapy With Reduced Doses of Pegfilgrastim.

BACKGROUND: Pegfilgrastim can be utilized to prevent neutropenia-associated complications in patients receiving myelosuppressive chemotherapy for breast cancer. A common adverse event associated with pegfilgrastim is bone pain. Clinicians may opt to reduce the dose of pegfilgrastim when administering it to patients with previous severe or refractory bone pain. There is limited and conflicting evidence with regard to the safety and efficacy of this practice. The purpose of this study was to investigate the impact of administering reduced doses of pegfilgrastim on neutropenia-associated outcomes in patients with breast cancer receiving myelosuppressive chemotherapy. METHODS: A retrospective chart review was conducted at a large, multistate health system with several different medical oncology practice sites. The primary outcome was the incidence of febrile neutropenia. Secondary outcomes included the incidence and severity of neutropenia, hospitalization for febrile, use of intravenous antimicrobials for febrile, delays in chemotherapy or dose reductions in chemotherapy secondary to neutropenia or febrile, rationale for dose reduction of pegfilgrastim, and improvement in bone pain. RESULTS: A total of 80 patients received reduced dose pegfilgrastim. Most patients had their doses reduced secondary to bone pain (54%) or leukocytosis (14%). One (1.25%) patient experienced febrile neutropenia that did not require hospitalization or intravenous antimicrobials. Chemotherapy treatment delays and dose reductions secondary to neutropenia or febrile neutropenia occurred in 1 (1.25%) and 2 (2.5%) patients, respectively. CONCLUSION: Reduced doses of pegfilgrastim in patients receiving myelosuppressive chemotherapy for breast cancer resulted in a low incidence of neutropenia-associated events, including febrile neutropenia and grade 3/4 neutropenia.

Rucaparib: A Poly(ADP-Ribose) Polymerase Inhibitor for BRCA-Mutated Relapsed Ovarian Cancer.

OBJECTIVE: To review the pharmacology, safety, efficacy, and the role of rucaparib in the treatment of relapsed, advanced ovarian cancer. SUMMARY: A total of 2 phase I/II trials and 1 phase II trial have evaluated the safety and efficacy of oral rucaparib in ovarian cancer. In patients with deleterious BRCA1/2 mutation, an overall response rate of 80% was achieved in the phase II trial Assessment of Rucaparib in Ovarian CancEr Trial 2 (ARIEL2). In the same trial, progression-free survival was higher in patients with BRCA1/2 mutation and BRCA wild types with high loss of heterozygosity (LOH) than BRCA wild types with low LOH. Rucaparib was found to be relatively well tolerated in clinical trials, with the most common adverse events being anemia, fatigue, and nausea. CONCLUSION: Rucaparib appears to be a safe and effective new option in the treatment of relapsed, advanced BRCA1/2 mutant ovarian cancer. The role of rucaparib in this setting will likely expand and be further elucidated as results from several ongoing studies become available.

Case series of docetaxel-induced dorsal hand-foot syndrome.

Palmar-plantar erythrodysesthesia, also known as hand-foot syndrome (HFS), is a well-known dermatologic adverse event that can occur with a variety of cytotoxic chemotherapies including fluoropyrimidines, cytarabine, liposomal doxorubicin, and taxanes. HFS often presents as painful erythemas and desquamation of the skin involving the palms of the hands and the soles of the feet. Three cases are presented of patients with breast cancer who received multiagent chemotherapy regimens containing docetaxel that developed an atypical presentation of HFS on the dorsal aspect of the hands and feet. All patients received supportive care to manage the symptoms of their dermatologic toxicity. Dorsal HFS improved with supportive care or dose reduction and resolved following completion of the docetaxel-based chemotherapy. Based on the temporal relationship of the event and previous reports, we found that docetaxel was the probable offending agent.

Poly (ADP-ribose) Polymerase Inhibitors in the Management of Ovarian Cancer: A Drug Class Review.

OBJECTIVE: To review the pharmacology, safety, efficacy, and role of poly adenosine diphosphate [ADP]-ribose polymerase (PARP) inhibitors in the treatment and maintenance of relapsed, advanced ovarian cancer. SUMMARY: A total of 3 phase 2 trials and 2 phase 3 trials were reviewed that evaluated the safety and efficacy of oral niraparib, olaparib, and rucaparib in patients with ovarian cancer. Progression-free survival (PFS) was evaluated in the maintenance setting for niraparib and olaparib, resulting in a PFS of 21.0 months and 8.4 months, respectively. Olaparib and rucaparib were evaluated in the treatment setting, producing a PFS of 9.4 months and 12.8 months, respectively. PFS was higher in patients with BRCA mutation when compared to patients with BRCA wild-type in both the maintenance and treatment setting across all trials evaluated. Niraparib, olaparib, and rucaparib were found to be relatively well tolerated in clinical trials, with the most common adverse events being anemia, fatigue, and nausea. CONCLUSION: PARP inhibitors appear to be a safe and effective new option in the treatment and maintenance of relapsed, advanced BRCA1/2 mutant ovarian cancer. This drug class will likely have an expanding role in ovarian cancer as further trial results are published.