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About - Melphalan

By mouth: Treats symptoms of plasma cell cancer (multiple myeloma) and ovarian cancer.

Injection: Treats symptoms of plasma cell cancer (multiple myeloma).

UsesSide effectsLatest evidence reviewsResearch summaries for consumersBrand names

Results: 1 to 20 of 37

Melphalan and prednisone versus melphalan, prednisone and thalidomide for elderly and/or transplant ineligible patients with multiple myeloma: a meta-analysis

Trials comparing efficacy of melphalan prednisone (MP) with MP plus thalidomide in transplant ineligible, elderly patients with multiple myeloma have provided conflicting evidence. Although there is agreement regarding improved response rates (RRs) and higher toxicity with the addition of thalidomide to MP, the impact on progression free survival (PFS) and overall survival (OS) is less clear. We performed a meta-analysis comparing efficacy of melphalan, prednisone and thalidomide (MPT) and MP by pooling results on RR, PFS and OS reported in all the identified randomized controlled trials (RCTs) under a random effects model. Overall, six prospective RCTs, with data extractable from five published trials (n=1571) [corrected] were identified. The pooled odds ratio of responding to therapy with MPT vs MP was 3.39 (P<0.001, 95% CI: 2.24-5.12). The pooled hazard ratios for PFS and OS were and 0.68 (P<0.001; 95% CI: 0.55-0.82) and 0.80 (P=0.07; 95% CI: 0.63-1.02), respectively, in favor of MPT. The odds ratios for high grade peripheral neuropathy and deep venous thrombosis were 6.6 and 2.4, respectively, in favour of MP. There was significant heterogeneity among the RCTs. Our meta-analysis demonstrates that in previously untreated, transplant ineligible, elderly myeloma patients, the addition of T to MP results in significantly improved RR and PFS with a trend towards improvement in OS compared with MP alone, but at a cost of significantly greater toxicity.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2011

Drug Class Review: Newer Antiemetics: Final Report Update 1 [Internet]

Nausea and vomiting are major concerns for patients undergoing chemotherapy, radiation therapy and surgery with general anesthesia. Risk factors associated with chemotherapy-induced nausea and vomiting include emetogenicity of the chemotherapy regimen, dose, speed of intravenous infusion, female gender, age under 50 years, history of ethanol consumption, and history of prior chemotherapy. Factors predictive of radiation therapy-induced nausea and vomiting include site of irradiation (in particular, total body irradiation and radiation fields that include the abdomen), total field size, dose per fraction, age, and predisposition for emesis (history of sickness during pregnancy or motion sickness). Female gender, a history of motion sickness or prior postoperative nausea and vomiting, nonsmoking status, and use of postoperative opioids have been suggested as factors predictive of postoperative nausea and vomiting. The objective of this review was to evaluate the comparative effectiveness and harms of newer antiemetic drugs including the 5-HT3 and NK-1 antagonists.

Drug Class Reviews - Oregon Health & Science University.

Version: January 2009
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The Clinical Effectiveness and Cost-Effectiveness of Bortezomib and Thalidomide in Combination Regimens with an Alkylating Agent and a Corticosteroid for the First-Line Treatment of Multiple Myeloma: A Systematic Review and Economic Evaluation

Multiple myeloma (MM) is the second most common haematological cancer in the UK. MM is not curable but can be treated with a combination of supportive measures and chemotherapy that aim to extend the duration and quality of survival. The majority of patients are not able to withstand intensive treatment, such as high-dose chemotherapy with autologous stem cell transplantation (SCT), and so they are offered single-agent or combination chemotherapy. Combination therapies typically include chemotherapy with an alkylating agent and a corticosteroid. More recently, combination therapies have incorporated drugs such as thalidomide (Thalidomide Celgene®, Celgene) and bortezomib (Velcade®, Janssen–Cilag).

Health Technology Assessment - NIHR Evaluation, Trials and Studies Coordinating Centre (UK).

Version: December 2011
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Hydroxyurea for the Treatment of Sickle Cell Disease

To synthesize the published literature on the efficacy, effectiveness, and toxicity of hydroxyurea (HU) when used for treatment of sickle cell disease (SCD); and to review the evidence regarding barriers to its use.

Evidence Reports/Technology Assessments - Agency for Healthcare Research and Quality (US).

Version: February 2008
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Safety of thalidomide in newly diagnosed elderly myeloma patients: a meta-analysis of data from individual patients in six randomized trials

Treatment with melphalan-prednisone-thalidomide improves the outcome of patients with multiple myeloma and is now considered a standard of care for patients not eligible for transplantation. However, this treatment is a major source of morbidity. A meta-analysis of data from individual patients (n=1680) in six randomized trials was performed, comparing the effects of melphalan-prednisone-thalidomide versus melphalan-prednisone. The main objective was to estimate the risk of serious adverse events and their impact on outcome. The primary endpoints were the 2-year cumulative incidence of grade 3-4 hematologic and non-hematologic toxicities. At least 75% of the grade 3-4 toxicities occurred during the first 6 months of treatment in both treatment groups. The cumulative incidence of grade 3-4 hematologic toxicities was higher in the melphalan-prednisone-thalidomide group than in the melphalan-prednisone group (28% versus 22%; HR 1.32, 95% CI 1.05-1.66) as was the cumulative incidence of non-hematologic toxicities (39% versus 17%, HR 2.78, 95% CI 2.21-3.50). Grade 3-4 non-hematologic toxicities were significantly increased in patients with poor Performance Status. Occurrence of grade 3-4 non-hematologic toxicities had a negative impact on both progression-free survival (HR 1.24, 95% CI 1.07-1.45) and overall survival, (HR 1.23, 95% CI 1.03-1.47). Besides toxicities, progression-free and overall survival were also negatively affected by advanced International Staging System stage, high creatinine levels and poor Performance Status. Age had a negative impact on survival as well. Although melphalan-prednisone-thalidomide improved outcome, it increased toxicities, especially non-hematologic ones. Serious non-hematologic toxicities, older age, poor Performance Status, and high creatinine levels negatively affected survival.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2013

Thalidomide versus bortezomib based regimens as first-line therapy for patients with multiple myeloma: a systematic review

The review concluded that was unclear whether thalidomide or bortezomib (both with melphalan and prednisone) was superior for treating patients with newly diagnosed multiple myeloma. Head-to-head comparisons were recommended. The review was limited in some respects, including a rather narrow search, but the authors? cautious conclusions appear justified.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2011

Isolated limb perfusion for malignant melanoma: systematic review on effectiveness and safety

This review assessed the effectiveness and safety of isolated limb perfusion for malignant melanoma and concluded that isolated limb perfusion was safe and effective in achieving clinical responses in patients with unresectable locally advanced melanoma of the limbs. Several potential limitations in the review process made the reliability of the authors' conclusions unclear.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2010

Second primary malignancies with lenalidomide therapy for newly diagnosed myeloma: a meta-analysis of individual patient data

BACKGROUND: Lenalidomide has been linked to second primary malignancies in myeloma. We aimed to pool and analyse available data to compare the incidence of second primary malignancies in patients with and without lenalidomide exposure.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2014

Ocular side effects following intravitreal injection therapy for retinoblastoma: a systematic review

This review concluded that significant ocular complications were uncommon following intravitreal injection therapy for retinoblastoma (malignant tumour of the retina), and this risk may be reduced further by the use of careful injection technique and standard dosing regimens. These conclusions appear likely to be reliable, and the review recommendations for research are appropriate.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2014

The clinical effectiveness and cost effectiveness of bortezomib and thalidomide in combination regimens with an alkylating agent and a corticosteroid for the first-line treatment of multiple myeloma: a systematic review and economic evaluation

This review concluded that bortezomib or thalidomide in combination with melphalan and prednisolone/prednisone could be considered more effective than melphalan and prednisolone/prednisone for the first-line treatment of multiple myeloma. Further head-to-head trials of bortezomib- and thalidomide-containing combination regimens were required. These conclusions reflect limitations in the evidence base and are likely to be reliable.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2011

Lenalidomide versus thalidomide based regimens as first-line therapy for patients with multiple myeloma

Thalidomide (T) and lenalidomide (R) have been used as first-line therapy for previously untreated myeloma. However, direct head-to-head comparison between them is lacking. We performed an indirect meta-analysis to assess the treatment effects of lenalidomide- versus thalidomide-based regimens using common comparators. A comprehensive literature search was undertaken. The initial search yielded 1345 citations, of which 11 randomized controlled trials (RCTs) enrolling 4162 patients met the inclusion criteria. Indirect comparison of lenalidomide versus thalidomide maintenance after autologous stem cell transplant (ASCT) showed a progression-free survival (PFS) benefit (hazard ratio [HR] 0.75, 95% confidence interval [CI] [0.67, 0.85], p < 0.001) but no survival difference (HR 0.83, [0.63, 1.09], p = 0.19) when using observation/placebo as the common comparator. Similarly, the indirect comparison of melphalan-prednisone plus lenalidomide followed by lenalidomide maintenance (MPR-R) versus melphalan-prednisone-thalidomide induction followed by thalidomide maintenance (MPT-T) showed a statistically significant PFS advantage for MPR-R (HR 0.53, 95% CI [0.46, 0.60], p < 0.001), but no difference for overall survival (OS) (HR 0.97, [0.81, 1.17], p = 0.74). Additionally, the significant heterogeneity among pooled studies for the outcome of discontinuation rate due to treatment-related adverse events between MPT-T and MPR-R subgroups (p = 0.007) indicated that the discontinuation rate from thalidomide trials seems to be higher than that from lenalidomide trials. In conclusion, lenalidomide seems to be a more potent and less toxic agent than thalidomide in the treatment of patients with multiple myeloma. Further, a direct head-to-head trial comparing lenalidomide versus thalidomide is clearly warranted.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2013

Outcomes of isolated limb perfusion in the treatment of extremity soft tissue sarcoma: a systematic review

BACKGROUND: Isolated limb perfusion (ILP) may provide a limb salvage option for locally advanced soft tissue sarcoma (STS) not amenable to local resection.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2013

Feasibility and safety of autotransplants with noncryopreserved marrow or peripheral blood stem cells: a systematic review

This review concluded that non-cryopreserved autotransplants are feasible and safe for patients undergoing high-dose chemotherapy for malignancy. The conclusions appear to be supported by the data but, owing to the absence of controlled evidence, the possibility of publication bias and the poor reporting of review methods, it is difficult to assess their reliability.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2007

Outcomes after Yttrium-ibritumomab tiuxetan-BEAM in diffuse large B-cell lymphoma: a meta-analysis

High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is a standard therapy in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) who are chemosensitive. The combination of carmustine, etoposide, cytarabine, and melphalan (BEAM) is commonly used as a conditioning regimen. The addition of yttrium-90 ((90) Y)-ibritumomab tiuxetan (Zevalin(®)) to BEAM (Z-BEAM) is increasingly being used to improve outcomes and overcome refractory disease. We conducted a literature review and meta-analysis in order to evaluate the clinical effects of Z-BEAM followed by ASCT in patients with DLBCL. A literature search was conducted for randomized controlled trials and observational studies of Z-BEAM as a conditioning regimen for ASCT in adult patients with DLBCL. Extracted data included baseline patient demographics, overall response (ORR), complete response (CR), overall survival (OS), progression-free survival (PFS), nonrelapse mortality (NRM), median time to ANC and platelet engraftment, and rate of myelodysplastic syndrome. Mixed-effects models were used to determine estimates. Ten studies (N = 328) were included in the meta-analysis. The 2-year OS and PFS were 84.5% (n = 328) and 67.2% (n = 285), respectively. Outcomes were superior in patients with nontransformed lymphoma. Posttransplant, ORR and CR rates were 72.6% and 68.5%, respectively. The NRM rate was 6.3% and the incidence rate of myelodysplastic syndrome was 2.5%. Two-year OS was significantly associated with pretransplant ORR (P = 0.008, τ(2) = 0). There was no significant association between PFS and pretransplant response. Z-BEAM is safe and effective as a conditioning regimen in relapsed/refractory DLBCL.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2014

Plasma Cell Neoplasms (Including Multiple Myeloma) Treatment (PDQ®): Health Professional Version

Expert-reviewed information summary about the treatment of plasma cell neoplasms (including multiple myeloma).

PDQ Cancer Information Summaries [Internet] - National Cancer Institute (US).

Version: June 24, 2014

Alkylating agents for Waldenstrom's macroglobulinaemia

Waldenstrom's macroglobulinaemia (WM) is an uncommon B‐cell lymphoproliferative disorder characterised by bone marrow infiltration and production of monoclonal immunoglobulin. It is a kind of non‐Hodgkin's lymphoma which can lead to death. Alkylating agents are believed to be effective in treatment of Waldenstrom's macroglobulinaemia for alleviating symptoms and elongating survival time. The review authors found one randomised controlled trial with 92 participants that considered fludarabine was superior to the alkylating agents‐containing regimen for pretreated/relapsed patients with Waldenstrom's macroglobulinaemia.

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: 2009

The clinical effectiveness and cost-effectiveness of bortezomib and thalidomide in combination regimens with an alkylating agent and a corticosteroid for the first-line treatment of multiple myeloma: a systematic review and economic evaluation

Multiple myeloma (MM) is the second most common haematological cancer in the UK, characterised by unregulated plasma cell proliferation. In England and Wales there are approximately 3600 new diagnoses recorded annually, and in 2007 most diagnoses were recorded in people aged 75–79 years. Symptoms and clinical features of MM include fatigue, bone pain and/or fracture, anaemia, the presence of M-protein in serum and/or urine, and hypercalcaemia. The aetiology of MM is unknown and malignant cells display a variety of cytogenetic abnormalities. Myeloma is not curable, but can be treated with a combination of supportive measures and chemotherapy. The aim is to extend the duration and quality of survival by alleviating symptoms and achieving disease control while minimising the adverse effects of the treatment. Survival of patients from diagnosis can vary from months to over a decade. Factors affecting prognosis include burden of disease, type of cytogenetic abnormality present, patient-related factors – such as age and performance status – and treatment response factors.

NIHR Health Technology Assessment programme: Executive Summaries - NIHR Evaluation, Trials and Studies Coordinating Centre (UK).

Version: 2011

Early treatment for early stage multiple myeloma may slow the disease progression but does not appear to improve survival

Multiple myeloma (MM) is cancer of the bone marrow. It causes bone destruction that leads to pain, spinal cord compression and fractures.In early stages, most people do not show any symptoms of MM. It is not clear whether it is better to start treatment with cancer drugs straight after diagnosis, or to wait until symptoms of the disease appear. The review of trials found that early treatment slows the progression of the disease. However, there is not enough evidence, due to too few studies conducted in patients with early stage myeloma to show that early treatment improves the survival of people with MM.

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: 2012

Combinations of anti‐cancer drugs to treat high‐risk cancers arising from the placenta, known as high‐risk gestational trophoblastic neoplasia (GTN)

GTN is a cancer that most often arises after a molar pregnancy but can arise after any type of pregnancy. Molar pregnancies occur due to abnormal growth of placental tissue that is usually benign and treated by evacuation of the womb (D&C). However, in less than 10% of molar pregnancies in the UK, the growth remains after D&C and transforms into a cancer (GTN) that needs treatment with anti‐cancer drugs (chemotherapy). GTN can be low‐risk or high‐risk. Anti‐cancer drugs are very effective, especially in low‐risk GTN, which is usually cured with single‐drug treatment. However, high‐risk GTN needs to be treated with combinations of anti‐cancer drugs for the best effect. These drugs can produce toxic side effects that are more likely to occur when used in combination with each other. The most commonly administered drug combination is abbreviated as EMA/CO, which stands for Etoposide, Methotrexate, Actinomycin D, Cyclophosphamide and Oncovin® (vincristine), but several other combinations are also in use.

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: 2014

Ovarian Low Malignant Potential Tumors Treatment (PDQ®): Health Professional Version

Expert-reviewed information summary about the treatment of ovarian low-malignant potential tumors.

PDQ Cancer Information Summaries [Internet] - National Cancer Institute (US).

Version: July 9, 2012

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