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Antineoplastic Drugs during Pregnancy
Published in “Bert” Bertis Britt Little, Drugs and Pregnancy, 2022
Melphalan (Alkeran) is a phenylalanine derivative of nitrogen mustard, and a bifunctional alkylating agent. It is an FDA-approved antineoplastic agent for treatment of multiple myeloma, ovarian, and breast carcinomas. Melphalan may also be used to treat chronic myelocytic leukemia, melanoma, osteosarcoma, soft tissue sarcoma, and thyroid cancers. The manufacturer reports that oral melphalan caused an increased frequency of congenital anomalies and embryonic death in rat models (Manufacturer product information). No studies of the use of this drug during pregnancy in humans are published. Melphalan is an alkylating agent with chemical effects (strong mutagenic and cytotoxic action) that strongly suggest it may be associated with an increased frequency of birth defects, and it should be avoided during pregnancy, especially during the first trimester.
Nucleic Acids as Therapeutic Targets and Agents
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Melphalan is licensed in many countries for the treatment of multiple myeloma, polycythemia vera, childhood neuroblastoma, and advanced ovarian adenocarcinoma and breast cancer, although in practice it is rarely used for ovarian adenocarcinoma, and no longer used for advanced breast cancer. In the UK it is recommended by NICE for the treatment of multiple myeloma (by mouth or IV), polycythemia vera (by mouth), or localized malignant melanoma or soft-tissue sarcoma of the extremities (by regional arterial perfusion).
Multiple myeloma
Published in Anju Sahdev, Sarah J. Vinnicombe, Husband & Reznek's Imaging in Oncology, 2020
Central venous catheters represent a potential source of bacteraemia (182). Melphalan is associated with increased risk of pancytopaenia, mucositis, and pulmonary complications (183–186). Conventional radiography and CT scanning are appropriate imaging investigations. High doses of corticosteroids may cause spinal fractures and avascular necrosis of the femoral heads (amongst other bones). MRI is useful for assessing both of these conditions. Abdominal discomfort resulting from constipation is a well-recognized side effect of thalidomide and can be readily assessed radiologically using a supine plain radiograph of the abdomen. A further reported side effect is interstitial pneumonitis, which can be identified on high-resolution CT (187). The drug bortezomib is associated with cytopaenia, and a decrease in platelet count to <50 000 mm3 occurs in almost 30% of patients, increasing the risk of haemorrhage (188). Other reported adverse effects are sensory neuropathy and pseudomembranous colitis (189). Side effects of intravenous bisphosphonates and newer bone modifying agents include acute-phase reactions, inflammatory reactions at the injection site, hypocalcaemia, hypophosphataemia, renal impairment, osteonecrosis of the jaw, and atypical fractures of the femur (190–194). Regular dental checkups in association with an orthopantomogram and a CT scan enable early diagnosis of osteonecrosis of the jaw (195). Peripheral neuropathy is a significant complication of multiple myeloma that can be caused by the disease itself or by certain therapies including thalidomide and bortezomib (54).
Role of immune checkpoint inhibitors in metastatic uveal melanoma: a single-center retrospective cohort study
Published in Acta Oncologica, 2023
Lize Vanaken, F.J. Sherida H. Woei-A-Jin, Rita Van Ginderdeuren, Christophe M. Deroose, Annouschka Laenen, Guy Missotten, Dietmar R. Thal, Oliver Bechter, Patrick Schöffski, Paul Clement
Treatments were categorized as ICI, other systemic treatments, local treatments or best supportive care (BSC) (i.e., no anti-cancer treatment). Since ICI was introduced in our hospital as treatment for MUM on August 1st, 2010, we refer to the period before this date as the pre-ICI era and the period afterwards as the ICI era. All patients were observed until data cutoff on August 1st, 2022. The category ‘other systemic treatments’ included chemotherapy, tyrosine kinase inhibitors and Tebentafusp. Local treatments included LDT and local therapies such as surgery and external beam radiotherapy for oligometastatic disease. In our center, the selective internal radiation therapy (SIRT) procedure consisted of injection of radioactive 90Yttrium microspheres in the common/right/left hepatic artery or smaller branches (tumoricidal dose >100 Gy). For trans-arterial embolization small particles without chemotherapeutic impregnation were used. High dose melphalan was used for isolated hepatic perfusion. Combination of ipilimulab and nivolumab followed by nivolumab monotherapy was counted as one treatment line unless interrupted by local therapies. Consecutive treatments with different classes of ICI upon disease progression were counted as separate treatment lines.
Guidelines for non-transplant chemotherapy for treatment of systemic AL amyloidosis: EHA-ISA working group
Published in Amyloid, 2023
Ashutosh D. Wechalekar, M. Teresa Cibeira, Simon D. Gibbs, Arnaud Jaccard, Shaji Kumar, Giampaolo Merlini, Giovanni Palladini, Vaishali Sanchorawala, Stefan Schönland, Christopher Venner, Mario Boccadoro, Efstathios Kastritis
Being on dialysis is per se not an indication for a specific regime choice but all drugs used require renal dose modification. Bortezomib generally does not need dose adjustment but it should administered after dialysis. Standard VCD has been used for several years in the management of patients with acute or chronic renal failure due to plasma cell disorders, either myeloma or AL amyloidosis or other monoclonal gammopathy related diseases. Melphalan requires dose adjustments and may be associated with unpredictable haematologic toxicity in patients with severe renal dysfunction. Among IMiDs, only lenalidomide requires dose modifications according to eGFR/CrCl; these are not necessary for pomalidomide or thalidomide. Daratumumab can be safely administered in patients with severe renal dysfunction or those undergoing dialysis, based on retrospective data from patients with AL amyloidosis or prospective data from myeloma patients. Retrospective data in relapsed/refractory AL have suggested that in patients with heavy proteinuria daratumumab may be less effective due to loss in urine [53] and this may also be a problem with other monoclonal antibody-based treatments in AL. PK data from the ANDROMEDA cohort suggests daratumumab kinetics were similar to that seen in multiple myeloma although specific analysis in patients with heavy proteinuria is not available [54]. When used intravenously, it may should be administered in a smaller fluid volume.
Palliative cytoreduction with low dose intravenous melphalan in patients with acute myeloid leukemia refractory to prior treatment
Published in Acta Clinica Belgica, 2022
Despite the recent evolution with many innovative targeted treatments, hyperproliferative crises will still occur in many patients during the course of their disease. In our center, low-dose intravenous melphalan is used as palliative cytoreductive therapy in order to rapidly reduce blast count and relieve or avoid symptoms of leukostasis. If used in low doses, melphalan is not associated with alopecia, nausea, catastrophic tumor lysis syndrome or other frequent complications of chemotherapy, but still effective within days. A rapid cytoreduction in patients with symptoms caused by hyperproliferative AML could temporarily improve the quality of life. In myelodysplastic syndrome or AML, daily low-dose oral melphalan has been reported to have a significant effect in palliative treatment [7–9]; however, no prior reports have described the use of intravenous low-dose melphalan as palliative cytoreductive treatment for AML.