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Chemotherapy in pregnancy
Published in Hung N. Winn, Frank A. Chervenak, Roberto Romero, Clinical Maternal-Fetal Medicine Online, 2021
Vincristine is a vinca alkaloid antimicrotubule agent derived from the periwinkle Catharanthus roseus plant. It is indicated for the treatment of choriocarcinoma, brain tumors, thyroid cancer, leukemia, lymphoma, sarcomas, and several other malignancies. As noted above, vincristine has been used in combination with bleomycin and other agents, delivering infants without abnormalities. Tewari et al. reported on the neoadjuvant treatment of cervical cancer with cisplatin and vincristine in two pregnant women, both of whom experienced significant reductions in tumor volume (19). No adverse fetal effects were noted. Bader et al. also reported on the use of cisplatin and vincristine in a patient for the neoadjuvant treatment of a cervical cancer beginning in the 23rd week of pregnancy (85). At 33 weeks, the patient then underwent a cesarean radical hysterectomy, delivering a normal infant. There have been some sporadic reports of atrial septal defects, renal hypoplasia, and pancytopenia following the use of vincristine in pregnancy (45,86,87). Several other authors have reported the successful use of vincristine, most frequently in combination with other agents, leading to the delivery and normal development of healthy infants (88,89).
Non-Hodgkin Lymphoma
Published in Pat Price, Karol Sikora, Treatment of Cancer, 2020
Piers Blombery, David C. Linch
A significant advance in the treatment of ALCL is the incorporation of brentuximab vedotin (BV) into both frontline and relapsed/refractory settings. BV is an anti-CD30 antibody conjugated to a potent antimicrotubule agent which has been demonstrated to improve progression-free and overall survival when substituted into the CHOP regimen in place of vincristine (BV-CHP).91 In patients with relapsed disease,92 the use of BV may facilitate bridging to either autologous or allogeneic stem cell transplantation and therefore the potential for long-term disease control. Targeting the ALK fusion protein in ALK-positive ALCL with ALK-inhibitors such as crizotinib is also emerging as a highly effective strategy in the relapsed/refractory setting.93
Lymphoma
Published in Anju Sahdev, Sarah J. Vinnicombe, Husband & Reznek's Imaging in Oncology, 2020
Sarah J Vinnicombe, Rodney J Hicks
More recently, there has been increasing interest in the role of biological therapies, for example the antibody-drug conjugate brentuximab vedotin, consisting of an anti-CD30 antibody combined with an antimicrotubule agent. This demonstrates high objective response rates in patients relapsing after ASCT and is recommended by the National Institute for Clinical Excellence (NICE) in this scenario (32,33). It is also used in anaplastic large-cell non-Hodgkin lymphoma (ALCL), another CD30-expressing lymphoma, and mantle cell lymphoma (34). Other very promising agents include the anti-PD-1 checkpoint inhibitors nivolumab and pembrolizumab.
Docetaxel-induced acute myositis: a case report with review of literature
Published in Journal of Chemotherapy, 2021
Sariya Wongsaengsak, Miguel Quirch, Somedeb Ball, Anita Sultan, Nusrat Jahan, Mohamed Elmassry, Shabnam Rehman
Docetaxel is a medication in the Taxane group. Docetaxel is an antimicrotubule agent that inhibits the reorganization of the microtubule network that is needed for mitosis, thereby leading to cancer cell apoptosis.1 Docetaxel was first approved by the Food and Drug Administration (FDA) in 1996 as a second-line treatment of locally advanced and metastatic breast cancer based on the positive results from clinical trials which showed that it was a highly effective antineoplastic agent for breast cancer.2 Since then, its indications have expanded to the treatment of many other solid tumors such as non small cell lung cancer, prostate cancer, gastric adenocarcinoma, and squamous cell carcinoma of head and neck.3 The well-established side effects of docetaxel are myelosuppression, severe neutropenia, peripheral neuropathy, fluid retention, and asthenia.1,2 The most commonly reported musculoskeletal adverse event is myalgia and joint pain. A few studies reported that 78%-87% of patients who have been exposed to taxanes experienced mild to moderate myalgia at some point in the course of treatment.1,4,5 Unfortunately, severe acute myositis remains an unusual complication. We report a case of acute myositis related to docetaxel in a patient with breast cancer.
Toxicities of novel therapies for hematologic malignancies
Published in Expert Review of Hematology, 2020
Florian Simon, Jorge Garcia Borrega, Paul J. Bröckelmann
ADCs allow the targeted delivery of a (usually cytotoxic) drug by conjugation to a MAB. Brentuximab vedotin (BV), an anti-CD30 antibody paired with the antimicrotubule agent monomethyl auristatin E (MMAE), was approved for r/r HL based on a single-arm phase II trial due to high ORR with complete responses in heavily pretreated patients [44]. Overall 55% of the patients experienced °3/4 toxicity. Neutropenia (19%) and peripheral polyneuropathy (PNP, 42%) accounted for the majority of relevant any grade events, with °3-4 PNP observed in 8% of patients. Very recently, the anti-CD79b ADC polatuzumab vedotin (pola), targeting a component of the B-cell receptor and linked to MMAE, was evaluated in r/r diffuse large B-cell lymphoma in combination with bendamustine and CD20-antibodies (BR, BG). Compared to standard BR treatment, patients treated with pola-BR had longer PFS and OS but also higher rates of °3-4 neutropenia (46% vs. 33%), anemia (28% vs. 18%), and thrombocytopenia (41% vs. 23%), but similar °3-4 infections (23% vs. 21%). PNP of °1-2 was observed in 43.6% of the patients, which similarly to BV was mostly reversible after treatment discontinuation [45]. In summary, ADCs are effective in targeted delivery of cytotoxic substances and mainly associated with PNP which should be assessed regularly and proactively by the treating physician. Dose reduction and delay are able to mitigate this clinically relevant toxicity and PNP frequently is reversible after end of treatment.
Efficacy of nab-paclitaxel in treating metastatic melanoma
Published in Expert Opinion on Pharmacotherapy, 2019
nab-Paclitaxel is a solvent-free human serum albumin-paclitaxel nanoparticle of approximately 130 nm in size, where the paclitaxel is present in a non-crystalline, amorphous state. Paclitaxel is an antimicrotubule agent that promotes the assembly of microtubules from tubulin dimers and stabilizes microtubules by preventing depolymerization. This stability results in the inhibition of the normal dynamic reorganization of the microtubule network that is essential for vital interphase and mitotic cellular functions. In addition, paclitaxel induces abnormal arrays or ‘bundles’ of microtubules throughout the cell cycle and multiple asters of microtubules during mitosis [7]. Upon intravenous administration of nab-paclitaxel, the nanoparticles dissociate rapidly into soluble, albumin bound paclitaxel complexes of approximately 10 nm in size. Albumin is known to mediate endothelial caveolar transcytosis of plasma constituents, and in vitro studies demonstrated that the presence of albumin in nab-paclitaxel enhances transport of paclitaxel across endothelial cells. It is hypothesized that this enhanced transendothelial caveolar transport is mediated by the gp-60 albumin receptor, and that there is enhanced accumulation of paclitaxel in the area of tumor due to the albumin-binding protein Secreted Protein Acidic Rich in Cysteine (SPARC) [7].