-
The Oncologist 2010Isolated limb perfusion (ILP) involves the administration of chemotherapy drugs directly into a limb involved by locoregional metastases. Unresectable locally advanced... (Review)
Review
BACKGROUND
Isolated limb perfusion (ILP) involves the administration of chemotherapy drugs directly into a limb involved by locoregional metastases. Unresectable locally advanced melanoma of the limbs represents one of the clinical settings in which ILP has demonstrated benefits.
METHODS
A systematic review of the literature on ILP for patients with unresectable locally advanced melanoma of the limbs was conducted. MEDLINE, EMBASE, and Cochrane database searches were conducted to identify studies fulfilling the following inclusion criteria: hyper- or normothermic ILP with melphalan with or without tumor necrosis factor (TNF) or other drugs providing valid data on clinical response, survival, or toxicity. To allocate levels of evidence and grades of recommendation the Scottish Intercollegiate Guidelines Network system was used.
RESULTS
Twenty-two studies including 2,018 ILPs were selected with a clear predominance of observational studies (90.90%) against experimental studies (9.10%). The median complete response rate to ILP was of 58.20%, with a median overall response rate of 90.35%. ILP with melphalan yielded a median complete response rate of 46.50%, against a 68.90% median complete response rate for melphalan plus TNF ILP. The median 5-year overall-survival rate was 36.50%, with a median overall survival interval of 36.70 months. The Wieberdink IV and V regional toxicity rates were 2.00% and 0.65%, respectively.
CONCLUSIONS
ILP is effective in achieving clinical responses in patients with unresectable locally advanced melanoma of the limbs. The disease-free and overall survival rates provided by ILP are acceptable. ILP is safe, with a low incidence of severe regional and systemic toxicity.
Topics: Antineoplastic Agents, Alkylating; Chemotherapy, Cancer, Regional Perfusion; Disease Progression; Extremities; Humans; Melanoma; Melphalan; Spain; Treatment Outcome
PubMed: 20348274
DOI: 10.1634/theoncologist.2009-0325 -
Annals of Hematology Aug 2009Polycythemia vera (PV) in children and adolescents is very rare. Data on clinical and laboratory evaluations as well as on treatment modalities are sparse. Here, we... (Review)
Review
Polycythemia vera (PV) in children and adolescents is very rare. Data on clinical and laboratory evaluations as well as on treatment modalities are sparse. Here, we report the long-term clinical course of a PV patient first diagnosed more than 40 years ago at age 12. In addition, after a systematic review of the scientific medical literature, clinical and hematological data of 35 patients (19 female and 17 male) from 25 previous reports are summarized. Three patients developed PV following antecedent hematological malignancies. Budd-Chiari syndrome was diagnosed in seven patients indicating a particular risk of young patients of developing this disorder. One patient presented with ischemic stroke, one patient with gangrene, and three patients with severe hemorrhage. Three patients died from disease-related complications. Hematocrit levels and platelet counts were not correlated with disease severity. Leukocytosis >15 x 10(9)/L was present in 9/35 patients and associated with a thromboembolic or hemorrhagic complication in seven patients. The few available data on molecular genetics and endogenous erythroid colony growth indicate changes comparable to those detectable in adult patients. Treatment varied enormously. It included aspirin, phlebotomy, hydroxycarbamide, busulfan, melphalan, pyrimethamine, and interferon-alpha. Two patients successfully underwent stem cell transplantation. Currently, it is impossible to treat an individual pediatric PV patient with an evidence-based regimen.
Topics: Adolescent; Budd-Chiari Syndrome; Child; Erythropoiesis; Hematologic Neoplasms; Hematologic Tests; Humans; Middle Aged; Polycythemia; Polycythemia Vera
PubMed: 19468728
DOI: 10.1007/s00277-009-0758-y -
Nefrologia : Publicacion Oficial de La... 2008We reviewed the literature in 2007 on 3 groups of systemic diseases affecting the kidney: lupic nephropathy (LN), small vessel vasculitis (SVV) and renal amyloidosis. A... (Review)
Review
We reviewed the literature in 2007 on 3 groups of systemic diseases affecting the kidney: lupic nephropathy (LN), small vessel vasculitis (SVV) and renal amyloidosis. A systematic review of 268 patients with LN pooled from 4 studies found that mycophenolic acid (MPA) in the induction phase caused more remissions and achieved greater renal survival than cyclophosphamide (CP), confirming it as a valid alternative to CP. Using a protocol including rituximab and MPA in the induction phase (14 days), MPA alone without corticoids is effective and safe in the maintenance phase. Rituximab has also been successfully used in CP-resistant forms of LN, where it reduces clinical activity and mesangial proliferation. Plasma exchanges achieve better results than bolus corticoids in SVS with severe renal failure. Complications are severe. Anti- TNF-alpha agents provide no benefit in this indication. Prolonged administration of low-dose corticoids reduces the incidence of relapses. MPA is an alternative to CP if this drug cannot be administered. Good results are achieved with rituximab in CP-resistant forms. According to a controlled trial, treatment of AL amyloidosis with dexamethasone and melphalan has equivalent results to highdose melphalan and rescue with hematopoietic stem cell transplant. In AA amyloidosis, eprosidate slows the rate of progression of renal failure.
Topics: Adrenal Cortex Hormones; Amyloidosis; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Combined Modality Therapy; Cyclophosphamide; Drug Therapy, Combination; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Kidney Diseases; Kidney Failure, Chronic; Lupus Nephritis; Melphalan; Mycophenolic Acid; Plasma Exchange; Randomized Controlled Trials as Topic; Recurrence; Rituximab; Vasculitis
PubMed: 18847427
DOI: No ID Found -
Journal of Thoracic Oncology : Official... Apr 2007This clinical practice guideline, based on a systematic review, evaluates chemotherapy options for patients with relapsed small cell lung cancer (SCLC). (Meta-Analysis)
Meta-Analysis Review
PURPOSE
This clinical practice guideline, based on a systematic review, evaluates chemotherapy options for patients with relapsed small cell lung cancer (SCLC).
METHODS
Relevant randomized trials and meta-analyses were identified through a systematic search of the literature. External feedback was obtained from practitioners in Ontario, and the guideline was approved by the provincial lung cancer disease site group.
RESULTS
Six randomized trials met the eligibility criteria and were included for review. One randomized phase III trial of oral topotecan versus no treatment in patients receiving best supportive care found topotecan to have a significant benefit in terms of 6-month survival and quality of life. A randomized phase III trial compared outcomes of carboplatin in patients receiving a combination of etoposide and cisplatin (EP) and found no significant improvement associated with carboplatin, although it was associated with significantly higher grade 3/4 thrombocytopenia. Two randomized trials directly compared chemotherapy regimens (intravenous [i.v.] topotecan versus cyclophosphamide, doxorubicin, and vincristine (CAV); and bis-chloro-ethylnitrosourea, thiotepa, vincristine, and cyclophosphamide (BTOC) versus EP), but these trials found no significant differences in terms of disease response or survival. I.v. topotecan was associated with significantly higher toxicities (grade 4 thrombocytopenia and grade 3/4 anemia) and greater improvement in patient-reported symptoms compared with CAV. Two randomized trials of topotecan-treated patients comparing route of administration (i.v. versus oral) found no significant differences in terms of disease response, survival, or quality of life, although oral administration was associated with increased grade 3 or 4 diarrhea in both trials.
CONCLUSION
Evidence on the clinical benefit of second-line therapy in SCLC is limited. Topotecan is the most studied agent in this population; it has a response and survival benefit in comparison with placebo, but it also has greater toxicity in comparison with CAV. To date, significant differences in terms of response and survival are not evident in studied chemotherapy options.
Topics: Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Small Cell; Clinical Trials, Phase III as Topic; Etoposide; Female; Humans; Infusions, Intravenous; Lomustine; Lung Neoplasms; Male; Maximum Tolerated Dose; Melphalan; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Ontario; Practice Guidelines as Topic; Prognosis; Randomized Controlled Trials as Topic; Salvage Therapy; Survival Analysis; Topotecan
PubMed: 17409809
DOI: 10.1097/01.JTO.0000263720.15062.51 -
Annals of Oncology : Official Journal... Apr 2007The objective of this systematic review is to examine the feasibility and safety of autologous noncryopreserved stem-cell transplants. This technique avoids the cost of... (Review)
Review
The objective of this systematic review is to examine the feasibility and safety of autologous noncryopreserved stem-cell transplants. This technique avoids the cost of establishing and maintaining a cryopreservation facility and may be of value for transplant centers in regions with limited economic resources. The primary outcome was the graft failure rate. In addition, a detailed description of the high-dose therapy regimens employed was undertaken. Secondary outcomes were transplant-related mortality and neutrophil and platelet engraftments times. Sixteen well-conducted nonrandomized studies met the eligibility criteria. Only two cases of graft failure (0.36%) occurred among 560 assessable patients receiving high-dose therapy and autotransplant for non-Hodgkin's lymphoma, Hodgkin's lymphoma, multiple myeloma, germ-cell tumors and acute leukemias. The most traditional high-dose schedules were used, although often modified to shorter regimens. High-dose melphalan appeared especially useful given its short half-life and was used to treat multiple myeloma by most groups. Secondary outcomes were comparable to those reported in the most relevant studies addressing standard (cryopreserved) autotransplant. According to this study, the use of autologous noncryopreserved hematopoietic progenitors to support patients undergoing high-dose therapy is feasible and safe.
Topics: Bone Marrow Transplantation; Cryopreservation; Humans; Leukemia; Lymphoma; Multiple Myeloma; Peripheral Blood Stem Cell Transplantation; Transplantation, Autologous
PubMed: 17355952
DOI: 10.1093/annonc/mdm069 -
Haematologica Jun 2004Perceiving the need for rigorous recommendations to facilitate decisions concerning the management of patients with multiple myeloma (MM), the Italian Society of... (Review)
Review
Management of multiple myeloma and related-disorders: guidelines from the Italian Society of Hematology (SIE), Italian Society of Experimental Hematology (SIES) and Italian Group for Bone Marrow Transplantation (GITMO).
OBJECTIVES
Perceiving the need for rigorous recommendations to facilitate decisions concerning the management of patients with multiple myeloma (MM), the Italian Society of Hematology (SIE) and the two affiliate societies (SIES and GITMO) commissioned a project to develop guidelines for the therapy of MM using evidence-based knowledge and consensus formation techniques.
METHODS
After a comprehensive systematic review of 1,450 papers, an Expert Panel formulated and graded sixty recommendations according to the supporting evidence. Evidence gaps were filled with twenty-two consensus-based statements. High grade recommendations (grade A) are reported below.
RESULTS
Treatment should be immediately initiated in MM patients with related organ damage: those patients aged below 65 years who do not have severe co-morbidities should receive autologous stem cell transplantation, while patients not candidates for autologous stem cell transplantation should receive oral melphalan and prednisone. Interferon-a should not be associated with conventional chemotherapy, but it can be offered with or without steroids as a maintenance therapy to patients who have reached a plateau phase. High-dose dexamethasone-containing regimens or high-dose dexamethasone alone are recommended as a first-line therapy when cytoreduction is urgently required (i.e., MM with spinal cord compression or with rapidly progressive renal failure). MM patients with moderate-to-severe anemia should receive erythropoietin, while patients with bone disease or osteopenia should receive long-term bisphophonates. Recommendations for the management of the clinical manifestations caused by the monoclonal protein (i.e. hyperviscosity, cast nephropathy, AL amyloidosis) and of solitary bone and extramedullary plasmacytoma were also elaborated.
CONCLUSIONS
A substantial proportion of clinical care for MM can be guided by evidence-based treatment recommendations.
Topics: Combined Modality Therapy; Disease Management; Evidence-Based Medicine; Humans; Italy; Multiple Myeloma; Societies, Medical
PubMed: 15194540
DOI: No ID Found -
The Cochrane Database of Systematic... 2003Early stage multiple myeloma (MM) represents about 20% of MM. Most of the patients are asymptomatic. Thus, it is far less dramatic than advanced disease and may require... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Early stage multiple myeloma (MM) represents about 20% of MM. Most of the patients are asymptomatic. Thus, it is far less dramatic than advanced disease and may require different treatment strategies. For these patients, it is not clear whether it is better to start chemotherapy right after the diagnosis or to delay the treatment until symptoms become obvious as the disease progresses.
OBJECTIVES
To identify and synthesize all available research evidence on whether early treatment intervention results in improved clinical outcomes when compared with observation alone. The main outcomes of interest that were examined included mortality, disease progression, response rate, and toxicity of early treatment.
SEARCH STRATEGY
Searches of the following electronic databases were undertaken: MEDLINE, EMBASE, CANCERLIT, LILLIACS and Cochrane Database of RCTs. We have recently compiled a comprehensive database of RCTs in myeloma. This search was updated and supplemented by hand-search of abstracts from main society meetings such as the ASH (American Society of Hematology), ASCO (American Society of Clinical Oncology), and EHA (European Haematology Association). In addition, we compared our list with a list of RCTs maintained by the Oxford Clinical Trial Service Unit.
SELECTION CRITERIA
Randomized controlled trials (RCT) with a parallel design that compared early versus deferred treatment of patients with early stage multiple myeloma based on Durie-Salmon (D-S) staging system. We also considered those trials that did not define early stage myeloma according to D-S staging system, but enrolled patients according to clinical uncertainty about the benefits of immediate intervention.
DATA COLLECTION AND ANALYSIS
Data synthesis was performed for all studies and according to the defined quality criteria. The first reviewer and the contact reviewer of this proposal independently extracted data. Disagreement was resolved by consensus. Revman software (ver 4.1) was used to combine results from all studies and expressed as an overall odds ratio or Peto's Odds Ratio, with 95% confidence interval.
MAIN RESULTS
Three trials were included with a total of 131 patients in each of the early treatment and deferred treatment groups. Early MM is asymptomatic stage I in these trials. All trials used standard Melphalan treatment but not stem cell transplantation. No statistically significant heterogeneity among the studies was detected. Beneficial effects of early treatment were seen in delay of myeloma progression (Peto's OR = 0.16, 95% CI: 0.09-0.29), and reduced vertebral compression (OR = 0.18, 95%CI: 0.02-1.59, NNT = 23, 95% CI: an NNT of 11, via infinity, to an NNH of 50). No significant effects on mortality and response rate were seen (Peto's OR = 1.11, 95% CI: 0.67-1.84, and OR = 0.63, 95% CI: 0.33-1.23, respectively). Early treatment may increase the risk of acute leukemia (Peto's OR = 3.20, 95% CI: 0.55-18.73, NNH = 44, 95% CI: an NNT of 63, via infinity, to an NNH of 15).
REVIEWER'S CONCLUSIONS
Early treatment of early stage multiple myeloma inhibits disease progression, and may reduce vertebral compression. However, early treatment may increase the risk of acute leukemia. However, the data on vertebral compression and leukaemic transformation may not be interpretable due to very small numbers. Based on the current evidence, mortality and response rate are not significantly affected by introducing early treatment in the progression of myeloma. However, it is quite possible that the lack of beneficial effects of early intervention in myeloma is a false negative result due to the paucity of the existing evidence. In addition, data on quality of life and toxicity were sparsely reported adding to additional difficulties about management decisions in early stage myeloma.
Topics: Disease Progression; Humans; Multiple Myeloma; Randomized Controlled Trials as Topic; Time Factors
PubMed: 12535504
DOI: 10.1002/14651858.CD004023