Administration Of Vinca Alkaloids Research Articles

Medicines Safety Update and PI changes for administration of vinca alkaloids

Medicines Safety Update and PI changes for administration of vinca alkaloids

Analysis of chemotherapy-induced peripheral neuropathy using the Japanese Adverse Drug Event Report database

Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse event associated with several antineoplastic drugs; however, the precise risks and time course of reactions of particular drugs are not clearly understood. The aim of this study was to evaluate the relationship between anticancer agents and CIPN development using data from the Japanese Adverse Drug Event Report (JADER) database and to characterize the time-to-onset and outcomes of CIPN. Chemotherapy-induced peripheral neuropathy was defined using the Medical Dictionary for Regulatory Activities preferred terms. Disproportionality analysis was performed by calculating the reporting odds ratio (ROR) with 95% confidence interval for signal detection. Data of nine Anatomical Therapeutic Chemical (ATC) drug categories correlated with CIPN development, in addition to the data of the time-to-onset and outcomes. Among 622,289 reports in the JADER database from April 2004 to March 2020, there were 1883 reports of adverse events corresponding to peripheral neuropathy. The ROR (95% confidence interval) for vinblastine, sorbent-based paclitaxel (sb-PTX), oxaliplatin, and bortezomib was 20.4 (12.5–33.4), 13.6 (11.9–15.7), 26.2 (23.6–29.1), and 30.8 (26.6–35.8), respectively. The median duration (interquartile range) to CIPN development after the administration of vinca alkaloids and analogues, taxanes, platinum compounds, and monoclonal antibodies was 11.0 (5.0–46.5), 22.5 (6.0–82.5), 22.0 (6.0–68.5), and 32.5 (11.3–73.8) days, respectively. The median duration (interquartile range) of sb-PTX and nanoparticle albumin-bound (nab)-PTX was 35.0 (7.0–94.0) and 5.5 (3.0–29.3) days, respectively. Our analysis of records in the JADER database revealed several drugs associated with a high risk for CIPN development. In particular, the development of CIPN after vinca alkaloid administration should be closely monitored for 2 weeks after administration. CIPN caused by nab-PTX showed significantly faster onset than that by sb-PTX. Patients who receive taxanes or monoclonal antibodies often do not show an improvement; accordingly, early treatment is required.

Abstract 3948: The sequential administration of vinca alkaloids and intermittent cyclophosphamide primes antigen-presenting and NK cells and significantly improves in vivo efficacy of anti-PD-L1 in triple-negative breast cancer models

Abstract Checkpoint inhibitors (CIs) have shown an unprecedented clinical activity in a large variety of cancer types, but only in a fraction of patients. To increase the number of responders, preclinical models are studied to define effective combinatorial regimens and the best window of therapeutic opportunities. We recently described a synergy between anti-PD-1 and -PD-L1 CIs and several types and dosages of chemotherapy in immunocompetent models of triple negative breast cancer (TNBC), likely due to unique effects of chemotherapeutics over circulating and tumor-infiltrating, suppressive, antigen-presenting and effector immune cell populations (Orecchioni et al, Br J Cancer 2018). To find a high-order drug combination, we have further studied by multiparametric flow cytometry and single-cell transcriptomic a panel of different chemotherapy drugs (including microtubular poisons, alkylating agents, topoisomerase inhibitors and antimetabolites) used in vivo at different dosages and schedule. Our aim was to define a combination, dose and schedule able to promote a) dendritic cell maturation, b) release and c) uptake of cancer-associated antigens from targeted neoplastic cells, d) cross-priming between antigen-presenting cells (APCs) and T cells, e) NK cell activation, and f) inhibition of suppressor immune cell populations. Vinca alkaloids vinblastine and vinorelbine (V), at low-medium dosages, were the most effective in a), b), c) and d). After V administration, Tregs were reduced, and circulating and tumor-infiltrating APCs showed a “maturation to activation” program with increased expression of several antigens including CD40, CD80, and CD86. The alkylating agent cyclophosphamide (CTX) targeted Tregs, mobilized APC progenitors, activated and increased the number of circulating and intratumoral NK cells. These effects were significantly increased when CTX was administered in an intermittent fashion (every 6 days) at low-medium doses. As the APC-NK cell axis has been recently found to be pivotal in CI-mediated, anti-tumor cell immunity, our data suggested a preclinical trial in immunocompetent orthotopic models of metastatic (post-mastectomy) BALB mice injected with 4T1 or EMT-6 TNBC cells. Among a large panel of different combinations and dosages, the sequential administration of V, intermittent CTX and anti-PD-L1 was the only able to completely abrogate TNBC local and metastatic growth, and this effect was not observed in T and NK cell-depleted mice. Taken together with recent data from randomized, combinatorial studies in TNBC patients (Schmid et al, NEJM 2018), our findings suggest that CIs might be included in future combinatorial regimens aimed at improving the percentage of patients receiving a clinical benefit and prolonging the duration of this benefit. Citation Format: Stefania Orecchioni, Loredana Vecchi, Paolo Falvo, Lucilla Luzi, Patrizia Mancuso, Chiara Camisaschi, Francesco Bertolini. The sequential administration of vinca alkaloids and intermittent cyclophosphamide primes antigen-presenting and NK cells and significantly improves in vivo efficacy of anti-PD-L1 in triple-negative breast cancer models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3948.

2016 Updated American Society of Clinical Oncology/Oncology Nursing Society Chemotherapy Administration Safety Standards, Including Standards for Pediatric Oncology

To update the American Society of Clinical Oncology (ASCO)/Oncology Nursing Society (ONS) Chemotherapy Administration Safety Standards and to highlight standards for pediatric oncology. The ASCO/ONS Chemotherapy Administration Safety Standards were first published in 2009 and updated in 2011 to include inpatient settings. A subsequent 2013 revision expanded the standards to include the safe administration and management of oral chemotherapy. A joint ASCO/ONS workshop with stakeholder participation, including that of the Association of Pediatric Hematology Oncology Nurses and American Society of Pediatric Hematology/Oncology, was held on May 12, 2015, to review the 2013 standards. An extensive literature search was subsequently conducted, and public comments on the revised draft standards were solicited. The updated 2016 standards presented here include clarification and expansion of existing standards to include pediatric oncology and to introduce new standards: most notably, two-person verification of chemotherapy preparation processes, administration of vinca alkaloids via minibags in facilities in which intrathecal medications are administered, and labeling of medications dispensed from the health care setting to be taken by the patient at home. The standards were reordered and renumbered to align with the sequential processes of chemotherapy prescription, preparation, and administration. Several standards were separated into their respective components for clarity and to facilitate measurement of adherence to a standard. As oncology practice has changed, so have chemotherapy administration safety standards. Advances in technology, cancer treatment, and education and training have prompted the need for periodic review and revision of the standards. Additional information is available at http://www.asco.org/chemo-standards.

2016 Updated American Society of Clinical Oncology/Oncology Nursing Society Chemotherapy Administration Safety Standards, Including Standards for Pediatric Oncology.

Purpose To update the ASCO/Oncology Nursing Society (ONS) Chemotherapy Administration Safety Standards and to highlight standards for pediatric oncology. Methods The ASCO/ONS Chemotherapy Administration Safety Standards were first published in 2009 and updated in 2011 to include inpatient settings. A subsequent 2013 revision expanded the standards to include the safe administration and management of oral chemotherapy. A joint ASCO/ONS workshop with stakeholder participation, including that of the Association of Pediatric Hematology Oncology Nurses and American Society of Pediatric Hematology/Oncology, was held on May 12, 2015, to review the 2013 standards. An extensive literature search was subsequently conducted, and public comments on the revised draft standards were solicited. Results The updated 2016 standards presented here include clarification and expansion of existing standards to include pediatric oncology and to introduce new standards: most notably, two-person verification of chemotherapy preparation processes, administration of vinca alkaloids via minibags in facilities in which intrathecal medications are administered, and labeling of medications dispensed from the health care setting to be taken by the patient at home. The standards were reordered and renumbered to align with the sequential processes of chemotherapy prescription, preparation, and administration. Several standards were separated into their respective components for clarity and to facilitate measurement of adherence to a standard. Conclusion As oncology practice has changed, so have chemotherapy administration safety standards. Advances in technology, cancer treatment, and education and training have prompted the need for periodic review and revision of the standards. Additional information is available at http://www.asco.org/chemo-standards .

Uneventful administration of vincristine in Charcot–Marie–Tooth disease type 1X

Charcot-Marie-Tooth (CMT) disease is the most common inherited peripheral neuropathy. Administration of vinca alkaloids is considered contraindicated in CMT because of the risk of life threatening acute neuropathy. We describe a 5-year-old patient with a family history of X-linked CMT1 who presented with Wilms tumour. Despite confirmation of a connexin 32 point mutation, the patient was treated with 40.5 mg/m(2) of vincristine with no clinical evidence of drug-related neuropathy. This case describes vincristine being safely administered to a patient with molecularly proven type CMT 1X, but in type 1A CMT vincristine is still contraindicated. An extensive literature review revealed no other series of cases in which vincristine administration in molecularly proven CMT 1X had been described. CMT should be excluded in any patient who develops a profound, acute neuropathy following vincristine, as many patients in the cases reviewed were asymptomatic prior to treatment.

The use of vinca alkaloids in preparation for splenectomy of corticosteroid refractory chronic immune thrombocytopenic purpura patients

Administration of vinca alkaloids (VA) to chronic corticosteroid refractory immune thrombocytopenia (ITP) patients results in a temporary increase of platelet count. The aim of the study was to evaluate the efficacy of vinca alkaloids in preparing adult corticosteroid refractory chronic ITP patients for splenectomy as well as to compare the costs of this method with costs of applying intravenous immunoglobulins. The study included 12 chronic ITP patients refractory to corticosteroids applied for 3-144 months. The patients were prepared for splenectomy with average 3.0 (from 1 to 4) 2-h intravenous infusions of vinca alkaloids at 7 day intervals. In eight patients, vincristin was used in a total dose of 6 mg (2 mg per infusion), in two patients, vinblastin was used in total dose of 30 mg (10 mg per infusion), and in two patients, vincristin and vinblastin infusions were administered alternatively. In nine of the 12 treated patients (75%) the platelet count increased to > or = 80 x 10(9)/l, which allowed safe splenectomy. Three patients unreactive to VA treatment were prepared for splenectomy with intravenous gammaglobulin infusions. Splenectomy was performed in 12 patients, in eight with laparoscopic method, in four with classic method. No complications during surgical intervention were observed. In none of the VA treated patients was myelosupression or liver or/and kidney dysfunction observed. Splenectomy resulted in normalization of platelet count in all patients after operation and in six of nine patients followed up for 10 months (on the average). Matching of VA costs with treatment efficacy and comparison with similar costs for intravenous immunoglobulin treatment revealed many fold lower costs of the former method.

Inadvertent intrathecal administration of vinca alkaloids

Inadvertent intrathecal administration of vinca alkaloids

The treatment of adult idiopathic thrombocytopenic purpura. Infusion of vinblastine in ITP.

16 adult idiopathic thrombocytopenic purpura (ITP) patients, with mean age 51 years, were treated by 5 weekly slow intravenous infusions of vinblastine (0.1 mg/kg). When a complete or partial response (CR or PR) was obtained, slow infusions were repeated at 2-weekly then monthly intervals, as maintenance therapy. In 4 cases with ITP of recent onset, but presenting contraindication or failure to prednisone and high dose intravenous immunoglobulins, CR was obtained in all patients after 4 to 15 days (mean 9.5). Only one of these patients relapsed. In 12 cases of refractory chronic ITP (of whom 10 had been splenectomized), there were 2 CR, 6 PR and 4 failures. The 8 responding patients had a mean interval to response of 20 days. The 6 PR were short and did not exceed 15 days. Our results do not support a superiority of this treatment compared to other modes of administration of vinca alkaloids in ITP (intravenous bolus, vinca loaded platelets).