-
European Journal of Medicinal Chemistry Aug 2022Cancer is an uncontrolled expansion of atypical cells in the body. These unusual cells are labelled as cancerous or malignant cells. Melphalan, an anticancer drug which... (Review)
Review
Cancer is an uncontrolled expansion of atypical cells in the body. These unusual cells are labelled as cancerous or malignant cells. Melphalan, an anticancer drug which is imperatively recognized under the class of alkylating agents. It exhibits broad spectrum antitumor activity, as observed in ovarian cancer, breast cancer, etc. However, it is mainly utilized in the management of multiple myeloma. Several studies across the globe suggest that resistance to melphalan is the major concern that leads to relapsed myeloma. In the present paper, several pivotal approaches to compensate resistance associated with melphalan have been discussed. Numerous chemical and formulation developments concerning melphalan to enhance its salient characteristics and targeted profile have also been portrayed. The rationale of the current article also summarizes the recent analytical methods, structure-activity relationship, pharmacokinetics, interactions, potential adverse effects along with medicinal updates of melphalan. Special attention is also laid on their synthetic developments viz. melphalan derivatives, conjugates and prodrugs along with encouraging insights and research findings.
Topics: Antineoplastic Agents, Alkylating; Drug Resistance, Neoplasm; Humans; Melphalan; Multiple Myeloma; Prodrugs; Structure-Activity Relationship
PubMed: 35665692
DOI: 10.1016/j.ejmech.2022.114494 -
Blood May 2022High-dose melphalan supported by autologous transplantation has been the standard of care for eligible patients with newly diagnosed multiple myeloma (MM) for >25 years.... (Review)
Review
High-dose melphalan supported by autologous transplantation has been the standard of care for eligible patients with newly diagnosed multiple myeloma (MM) for >25 years. Several randomized clinical trials have recently reaffirmed the strong position of transplantation in the era of proteasome inhibitors and immunomodulatory drugs combinations, demonstrating a significant reduction of progression or death in comparison with strategies without transplantation. Immunotherapy is currently changing the paradigm of MM management, and daratumumab is the first-in-class human monoclonal antibody targeting CD38 approved in the setting of newly diagnosed MM. Quadruplets have become the new standard in transplantation programs, but outcomes remain heterogeneous, with various response depth and duration. The development of sensitive and specific tools for disease prognostication allows the consideration of strategies adaptive to dynamic risk. This review discusses the different options available for the treatment of transplantation-eligible patients with MM in frontline setting.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bortezomib; Humans; Melphalan; Multiple Myeloma; Proteasome Inhibitors; Transplantation, Autologous
PubMed: 34788422
DOI: 10.1182/blood.2020008735 -
Scientific Reports Aug 2023Breast cancer is the second most common type of cancer worldwide and the leading cause of cancer death in women. Dietary bioactive compounds may act at different stages...
Breast cancer is the second most common type of cancer worldwide and the leading cause of cancer death in women. Dietary bioactive compounds may act at different stages of carcinogenesis, including tumor initiation, promotion, and progression. Spices have been used for thousands of years and have many bioactive compounds with chemopreventive and chemotherapeutic properties. Curcumin has a multitude of beneficial biological properties, including anti-inflammatory and anticancer effects. This study investigated the effects of cotreatment with curcumin and the chemotherapeutic drug melphalan in cultured MDA-MB-231 breast cancer cells. When used alone, both curcumin and melphalan had a cytotoxic effect on breast cancer cells. Combined treatment with 11.65 µM of curcumin and 93.95 µM of melphalan (CURC/MEL) reduced cell viability by 28.64% and 72.43% after 24 h and 48 h, respectively. CURC/MEL reduced the number of colony-forming units and increased ROS levels by 1.36-fold. CURC/MEL alter cell cycle progression, induce apoptosis, and upregulate caspases-3, -7, and -9, in MDA-MB-231 cells. Cotreatment with curcumin and melphalan have anti-breast cancer cells effects and represent a promising candidate for clinical testing.
Topics: Female; Humans; Melphalan; Curcumin; Breast Neoplasms; Cell Cycle Checkpoints; Apoptosis
PubMed: 37596331
DOI: 10.1038/s41598-023-40535-5 -
Acta Haematologica 2020AL amyloidosis is a systemic amyloidosis and is associated with an underlying plasma cell dyscrasia. High-dose intravenous melphalan and autologous stem cell... (Review)
Review
AL amyloidosis is a systemic amyloidosis and is associated with an underlying plasma cell dyscrasia. High-dose intravenous melphalan and autologous stem cell transplantation was developed for the treatment of AL amyloidosis in the early 1990s and was prompted by its success in myeloma. This application has evolved significantly over the past three decades. This review provides a comprehensive assessment of eligibility criteria, stem cell collection, and mobilization strategies and regimens, risk-adapted melphalan dosing, role for induction and consolidation therapies as well as long-term outcome with respect to survival, hematologic response and relapse as well as organ responses following stem cell transplantation. Continued efforts to refine patient selection and management, and incorporate novel anti-plasma cell agents in combination or sequentially to further improve outcomes in AL amyloidosis are also discussed.
Topics: Combined Modality Therapy; Disease Management; Hematopoietic Stem Cell Mobilization; Humans; Immunoglobulin Light-chain Amyloidosis; Melphalan; Myeloablative Agonists; Organ Specificity; Peripheral Blood Stem Cell Transplantation; Postoperative Care; Transplantation Conditioning; Transplantation, Autologous; Treatment Outcome
PubMed: 32248194
DOI: 10.1159/000506498 -
Leukemia & Lymphoma Nov 2020Multiple myeloma (MM) is a chronically managed blood cancer with a median age of 69 years at the time of diagnosis. Although high dose melphalan and autologous stem... (Review)
Review
Multiple myeloma (MM) is a chronically managed blood cancer with a median age of 69 years at the time of diagnosis. Although high dose melphalan and autologous stem cell transplantation (ASCT) remains a standard of care for eligible patients, more than half of the newly diagnosed MM patients are deemed ineligible due to comorbidities or complications of the disease by itself. In this setting, where ASCT is deemed inappropriate, patients could still achieve durable and deep responses if given the appropriate treatment plan. The key concepts of optimizing induction and maintenance strategies while minimizing side-effects are discussed in this review, especially in the context of employing novel agent combinations. It is important to understand the balance between safety and efficacy for each regimen, utilizing maintenance strategy and the best supportive care measures (bone health, infection prevention, and treatment, pain management, etc.). Here, we examine the evidence behind each of those principles and review results from clinical trials for transplant-ineligible (TI) MM.
Topics: Aged; Hematopoietic Stem Cell Transplantation; Humans; Melphalan; Multiple Myeloma; Transplantation, Autologous
PubMed: 32623918
DOI: 10.1080/10428194.2020.1786558 -
Leukemia Aug 2021The introduction of whole genome and exome sequencing partnered with advanced bioinformatic pipelines has allowed the comprehensive characterization of mutational... (Review)
Review
The introduction of whole genome and exome sequencing partnered with advanced bioinformatic pipelines has allowed the comprehensive characterization of mutational processes (i.e., mutational signatures) in individual cancer patients. Studies focusing on multiple myeloma have defined several mutational processes, including a recently identified mutational signature (called "SBS-MM1") directly caused by exposure to high-dose melphalan (i.e., autologous stem cell transplant). High-dose melphalan exposure increases both the overall and nonsynonymous mutational burden detected between diagnosis and relapse by ~10-20%. Nevertheless, most of these mutations are acquired within the heterochromatin and late-replicating regions, rarely involving key myeloma driver genes. In this review, we summarize key studies that made this discovery possible, and we discuss potential clinical implications.
Topics: Humans; Melphalan; Multiple Myeloma; Mutagenesis; Mutagens; Mutation; Neoplasm Proteins
PubMed: 34012133
DOI: 10.1038/s41375-021-01293-3 -
RoFo : Fortschritte Auf Dem Gebiete Der... Jan 2023Percutaneous hepatic perfusion (CS-PHP) is a treatment option for primary and secondary liver neoplasms and subject of intensive research. This present article provides...
BACKGROUND
Percutaneous hepatic perfusion (CS-PHP) is a treatment option for primary and secondary liver neoplasms and subject of intensive research. This present article provides an overview of CS-PHP regarding patient safety, feasibility and effectiveness based on recent studies.
METHOD
We performed a PubMed search including the search terms chemosaturation, hepatic chemosaturation, percutaneous perfusion and melphalan.
RESULTS AND CONCLUSION
CS-PHP is a promising procedure for the treatment of uveal melanoma and cholangiocellular carcinoma. There are insufficient data regarding the effectiveness of CS-PHP with respect to other tumor entities. Since CS-PHP can be accompanied by multiple transient side effects and complications, close interdisciplinary cooperation is necessary.
KEY POINTS
· Chemosaturation of the liver is a safe procedure.. · CS-PHP is a potent therapy for hepatic metastatic ocular melanoma and cholangiocellular carcinoma.. · The procedure requires close interdisciplinary coordination.. · CS-PHP is a repeatable and thus long-term therapeutic option for some patients..
CITATION FORMAT
· Ebel S, Struck MF, van Boemmel F et al. Chemosaturation of the Liver - an Update. Fortschr Röntgenstr 2023; 195: 30 - 37.
Topics: Humans; Chemotherapy, Cancer, Regional Perfusion; Melphalan; Liver Neoplasms; Cholangiocarcinoma
PubMed: 35977553
DOI: 10.1055/a-1858-3418 -
Expert Opinion on Investigational Drugs Oct 2020The overall survival of patients with multiple myeloma has improved with the advent of novel agents; however, multiple myeloma remains incurable. Combinations of... (Review)
Review
INTRODUCTION
The overall survival of patients with multiple myeloma has improved with the advent of novel agents; however, multiple myeloma remains incurable. Combinations of standard-of-care agents such as immunomodulators, proteasome inhibitors, and anti-CD38 monoclonal antibodies are increasingly used in earlier lines of therapy. Patients with disease that is refractory to multiple novel agents represent a population with high unmet medical need and for whom therapies with new mechanisms of action could be beneficial. Melphalan flufenamide (melflufen) has demonstrated encouraging activity in patients with relapsed and refractory multiple myeloma.
AREAS COVERED
This review provides an overview of the mechanism of action of melflufen, a first-in-class peptide-drug conjugate that targets aminopeptidases and rapidly delivers alkylating agents into tumor cells. It reviews key Phase I and II clinical trial data for melflufen in combination with dexamethasone as well as in triplet combinations with daratumumab or bortezomib. The safety profile of melflufen, which is characterized primarily by clinically manageable hematologic adverse events, is described.
EXPERT OPINION
Melflufen has potential to fill a gap in the myeloma treatment landscape by providing a new mechanism of action with clinically meaningful efficacy and a favorable safety profile in patients refractory to multiple novel agents.
Topics: Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Humans; Melphalan; Multiple Myeloma; Phenylalanine; Recurrence; Survival Rate
PubMed: 32924646
DOI: 10.1080/13543784.2020.1808884 -
Clinical Lymphoma, Myeloma & Leukemia Jun 2023In the global phase 3 ALCYONE trial, daratumumab plus bortezomib/melphalan/prednisone (D-VMP) improved outcomes versus VMP in transplant-ineligible newly diagnosed... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
In the global phase 3 ALCYONE trial, daratumumab plus bortezomib/melphalan/prednisone (D-VMP) improved outcomes versus VMP in transplant-ineligible newly diagnosed multiple myeloma (NDMM) patients. Here, we report the primary analysis of the phase 3 OCTANS trial of D-VMP versus VMP in transplant-ineligible Asian NDMM patients.
PATIENTS AND METHODS
In total, 220 patients were randomized (2:1) to receive 9 cycles of VMP (bortezomib 1.3 mg/m subcutaneously twice weekly in Cycle 1 and weekly in Cycles 2 to 9; melphalan 9 mg/m orally; and prednisone 60 mg/m orally on Days 1 to 4 of each cycle) ± daratumumab 16 mg/kg intravenously weekly in Cycle 1, every 3 weeks in Cycles 2 to 9, and every 4 weeks thereafter until disease progression.
RESULTS
After a median follow-up of 12.3 months, very good partial response or better rates (primary endpoint) were 74.0% versus 43.2% with D-VMP versus VMP (odds ratio, 3.57; 95% confidence interval [CI], 1.99-6.43; P < .0001). Median progression-free survival (PFS) with D-VMP versus VMP was not reached versus 18.2 months (hazard ratio, .43; 95% CI, .24-.77; P = .0033); 12-month PFS rates were 84.2% versus 64.6%. The most frequent grade 3/4 treatment-emergent adverse events with D-VMP/VMP were thrombocytopenia (46.5%/45.1%), neutropenia (39.6%/50.7%), and leukopenia (31.3%/36.6%).
CONCLUSION
D-VMP demonstrated a favorable benefit/risk profile in transplant-ineligible Asian NDMM patients. This trial was registered at www.
CLINICALTRIALS
gov as #NCT03217812.
Topics: Humans; Multiple Myeloma; Bortezomib; Melphalan; Prednisone; Antineoplastic Combined Chemotherapy Protocols; Thrombocytopenia; Treatment Outcome
PubMed: 37024420
DOI: 10.1016/j.clml.2023.02.009 -
Pediatric Blood & Cancer Jun 2021Appropriate high-dose chemotherapy (HDC) for high-risk neuroblastoma has not yet been established. In Japan, a unique HDC regimen that comprises two cycles of a total of...
BACKGROUND
Appropriate high-dose chemotherapy (HDC) for high-risk neuroblastoma has not yet been established. In Japan, a unique HDC regimen that comprises two cycles of a total of 800 mg/m of thiotepa and a total of 280 mg/m of melphalan is widely utilized.
METHODS
To evaluate the safety and efficacy of this thiotepa-melphalan high-dose therapy for high-risk neuroblastoma, we reviewed the medical records of 41 patients with high-risk neuroblastoma who underwent this regimen followed by autologous peripheral blood stem cell rescue between 2002 and 2012. MYCN-amplified high-risk neuroblastomas were observed in 23 patients. All patients underwent intensive multidrug induction chemotherapy, but none underwent anti-GD2 antibody immunotherapy. The primary tumor was resected at the adequate time point.
RESULTS
The median follow-up duration for living patients was 9.2 years (range 5.5-14.0 years). The 5-year event-free survival (EFS) and overall survival from treatment initiation were 41.5 ± 7.7% and 56.1 ± 7.8%, respectively. The 5-year EFS of MYCN-amplified high-risk neuroblastoma patients was 60.9 ± 10.2%, which was significantly superior compared with those with MYCN-nonamplified high-risk neuroblastoma (16.7 ± 8.8%; p < .001). MYCN amplification was the most favorable prognostic factor for EFS (hazard ratio = 0.29; 95% confidence interval = 0.12-0.66). Of the 41 patients, three died because of regimen-related toxicity (infection, n = 2; microangiopathy, n = 1).
CONCLUSION
The thiotepa-melphalan high-dose therapy with thiotepa and melphalan may be effective for high-risk neuroblastoma. However, this regimen is toxic and warrants special attention in clinical practice.
Topics: Antineoplastic Combined Chemotherapy Protocols; Disease-Free Survival; Humans; Infant; Melphalan; N-Myc Proto-Oncogene Protein; Neuroblastoma; Thiotepa; Transplantation, Autologous
PubMed: 33788375
DOI: 10.1002/pbc.28896