Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thalidomide has several mechanisms of action: a hypnosedative effect, several immuno-modulatory properties and an anti-angiogenic action. Thalidomide has been used in several cutaneous inflammatory disorders (such as erythema nodosum leprosum in lepromatous leprosy, cutaneous lupus erythematosus, severe aphtosis), cancers (relapsed/refractory multiple myeloma) and inflammatory conditions. Several side effects are associated with thalidomide: teratogenicity, peripheral neuropathy and deep venous thrombosis; some are minor, such as somnolence or abdominal pain and endocrinologic disturbances. Use of thalidomide is strictly controlled with close adherence to a birth control program and close monitoring for early development of peripheral neuropathy.
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PMID:[Thalidomide: new indications for an old drug]. 1593 72

Experimental studies have demonstrated that thalidomide has anti-tumor activity mediated by blockage of angiogenesis, with clinical efficacy in multiple myeloma, glioblastoma multiforme, and renal cell cancer. We investigated the therapeutic activity and toxicity of thalidomide in patients with progressive metastatic breast cancer pretreated with chemotherapy. Inclusion criteria were metastatic breast cancer in progression of disease after at least two lines of chemotherapy, age > or = 18 years, performance status < or = 2, and adequate hematologic, renal, and hepatic functions. Twelve patients entered the study, eight of whom were pretreated with three or more lines of chemotherapy (66.7%). Thalidomide was well tolerated: the most common side effects were constipation and somnolence (58.3% of patients). No objective response or durable stable disease was observed. Median time to progression and median overall survival were 8 weeks (range, 4-10 weeks) and 16 weeks (range, 8-54 weeks), respectively. In conclusion, thalidomide is an ineffective treatment in patients with progressive metastatic breast cancer heavily pretreated with chemotherapy.
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PMID:Thalidomide is inactive in heavily pretreated patients with metastatic breast cancer. 1605 69

The feasibility and efficacy of a combination of thalidomide, incadronate, and dexamethasone (TID) were studied in 12 patients with relapsed or refractory multiple myeloma. The protocol, consisting of 300 mg/day of thalidomide administered orally, intravenous incadronate (10 mg/day) administered weekly, and 12 mg/day dexamethasone for 4 days, was repeated every 3 weeks. Evaluations of efficacy and toxicity were carried out every 3 weeks and were continued for 3 cycles. Three patients were excluded during the study because of apnea, severe somnolence, and pancytopenia. Of 9 evaluated patients, the partial responses achieved in 3 patients and the minor responses achieved in 4 patients corresponded to a response rate of 78% according to the criteria of the European Group for Blood and Marrow Transplantation. In addition, painful osteolytic symptoms improved rapidly after 1 cycle of TID therapy in the 10 patients evaluated. These data suggest that TID is a feasible and promising therapeutic approach for refractory and relapsed multiple myeloma.
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PMID:Combination therapy with thalidomide, incadronate, and dexamethasone for relapsed or refractory multiple myeloma. 1620 98

Thalidomide represents a recent and innovative therapeutic approach in multiple myeloma. Main toxicity usually consists in somnolence, constipation, peripheral neuropathy and deep vein thrombosis, but, unlike alkylating agents, thalidomide is reported to rarely induce severe hematologic toxicity. The majority of patients developing neutropenia are heavily pretreated with three or more lines of chemotherapy. Here, we report, for the first time, clinical and laboratory data of a 66-year-old female patient with multiple myeloma at diagnosis who, after 4 weeks of thalidomide treatment, developed a grade 4 WHO neutropenia with septicemia. A brief review of the literature and suggestions for possible predictive factors of this toxicity are made.
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PMID:Low-dose thalidomide-induced agranulocytosis in a multiple myeloma patient treated at diagnosis. 1626 90

The activity of thalidomide in relapsed or refractory multiple myeloma is widely accepted but not yet demonstrated in a randomised-controlled trial. A systematic review of the published clinical trials of these patients could reduce the possible bias of single phase-II studies. A systematic search identified 42 communications reporting on 1674 patients. Thirty-two trials used an escalating dosing regimen and four a fixed dose regimen (one dose with 50 mg/d, three doses with 200 mg/d). The target dose in the dose escalating trials was 800 mg/d in 17 trials, 400-600 mg/d in 10 and 200 mg/d in one trial. The intention-to-treat population for efficacy was 1629 patients with a median age of 62 years. The complete and partial (>50% reduction in monoclonal protein) response rate was 29.4% (95%-confidence interval, 27-32%). The rates for minor responses or stable disease were 13.8% (12-16%) and 11.0% (9-13%). Progressive disease was reported in 9.9% (8-11%). The median overall survival from all trials was reported at 14 months. Severe adverse events (grade III-IV) included somnolence 11%, constipation 16%, neuropathy 6%, rash 3%, thrombo-embolism 3%, cardiac 2%. In conclusion, thalidomide monotherapy achieved complete and partial responses in 29.4% of patients with relapsed or refractory multiple myeloma.
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PMID:A systematic review of phase-II trials of thalidomide monotherapy in patients with relapsed or refractory multiple myeloma. 1644 31

Conventional IV chemotherapy regimens used for induction chemotherapy or salvage therapy in the treatment of multiple myeloma (MM) are cumbersome, with a negative impact on patient quality of life. A number of new oral drugs, including immunomodulatory agents such as thalidomide and lenalidomide, have demonstrated potent antimyeloma activity in relapsed and refractory as well as newly diagnosed MM. Clinically, response rates of 56%-72% have been reported with the combination of thalidomide and dexamethasone in patients with newly diagnosed disease; however, the combination is associated with a higher incidence of side effects, including constipation, somnolence, peripheral neuropathy, and thromboembolic complications. In contrast, preliminary safety and efficacy data from clinical studies of lenalidomide show promise. Response rates as high as 83% have been reported in patients with newly diagnosed MM, and the most common adverse event is manageable myelosuppression, which is reversible with dose reduction. Lenalidomide has different toxicities than thalidomide, exhibiting greater myelosuppression but virtually no constipation, somnolence, or peripheral neuropathy. Oncology nurses play a key role in monitoring patients for side effects and pain control and educating them about emerging treatment options. This article reviews the nursing experience with oral agents in the treatment of MM.
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PMID:Advances in oral therapy in the treatment of multiple myeloma. 1692 5

Thalidomide has several mechanisms of action: several immuno-modulatory properties, an anti-angiogenic action and a hypnosedative effect. Thalidomide has been used in several cutaneous inflammatory disorders (such as erythema nodosum leprosum in lepromatous leprosy, cutaneous lupus erythematosus, severe aphtosis), cancers (relapsed/refractory multiple myeloma) and inflammatory conditions. Several side effects are associated with thalidomide; some are major: teratogenicity, peripheral neuropathy and deep venous thrombosis; some are minor, such as somnolence or abdominal pain and endocrinologic disturbances. Use of thalidomide is strictly controlled with close adherence to a birth control program and close monitoring for early development of peripheral neuropathy.
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PMID:[The revival of thalidomide: an old drug with new indications]. 1727 97

Hepatocellular carcinoma (HCC) is a hypervascular tumour, which overexpresses vascular endothelial growth factor. Thalidomide is an antiangiogenic agent with activity in refractory multiple myeloma. The purpose of this multi-centre phase II study was to evaluate the efficacy and toxicity of thalidomide in patients with advanced HCC. From February 2000 to November 2001, 37 patients with histologically proven, bi-dimensionally measurable advanced, unresectable HCC were enrolled. The starting dose of Thalidomide was 100 mg per day and escalated weekly by 100 mg to a maximum dose of 800 mg/day according to individual patient tolerance. Radiological tumour response and treatment related toxicities were prospectively assessed. Thirty-seven patients were evaluable for toxicity and 24 patients were evaluable for response. The median Thalidomide dose was 400 mg/day. There was no complete response (CR). One patient had a radiological partial response (PR) (3%; 95% confidence interval [95% CI], 0% to 8%) and six (16%) patients had stable disease for more than 6 months. Somnolence and fatigue were the most common side effects, occurring in 84% and 73% of patients respectively. Thalidomide monotherapy is tolerable and associated with modest antitumour activity in advanced HCC.
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PMID:Multi-centre phase II trial of Thalidomide in the treatment of unresectable hepatocellular carcinoma. 1745 75

The potential synergistic anti-myeloma effect for thalidomide combining with interferon alpha was not yet clear clinically. From March 2001 to January 2004, a total of 28 heavily pretreated multiple myleoma (MM) patients were enrolled in this open-labeled, randomized Phase II study. Patients with refractory MM were randomized to receive either thalidomide alone (200 mg/day up to the maximum dose 800 mg/day, arm B) or the combination of thalidomide and interferon alpha (3 MIU/m(2) subcutaneous injection 3 times weekly, arm A). The objective of this study was to compare the safety and efficacy of thalidomide alone to combined regimen. The patients' characteristics were similar between the 2 arms. However, the average treatment duration was significantly longer in the arm B than the arm A (236 days versus 101 days, p = 0.029). Serum levels of paraprotein decline >/= 25 percent were obtained in 6 of 12 patients (50.0 percent) treated with arm B and 3 of the 16 patients (18.8 percent) treated with arm A. The estimated time to event was 7.9 months (95 percent confidence interval [95%CI], 0.5-15.4) for arm B and 1.5 months (95%CI, 0.0-3.4) for arm A (log-rank test, p = 0.0193). The major adverse events in both arms consisted of neutropenia, anemia, thrombocytopenia, constipation, somnolence, and skin rash. Our study showed that thalidomide alone was effective and tolerated in patients with relapsed or refractory MM. The thalidomide combined with interferon alpha resulted in a lower frequency of paraprotein response, shorter treatment-duration and 25 percent of patients' refusing rate. It may be concluded that the combined regimen is not well tolerated in our patients and needed to be further evaluated in the future.
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PMID:Randomized Phase II trial of thalidomide alone versus thalidomide plus interferon alpha in patients with refractory multiple myeloma. 1753 Apr 83

For many years the treatment of multiple myeloma was limited to such regimens as melphalan-prednisone, high-dose dexamethasone, and vincristine-doxorubicin-dexamethasone (VAD). These combinations provided response rates of 45-55%, with complete remission rates of up to 10%. With the advent of thalidomide- and bortezomib-based combinations, response rates to induction therapy have risen to 85-95% in previously untreated patients and are associated with complete remission rates up to 25%. However, these agents are associated with such side-effects as somnolence, constipation and neuropathy. Lenalidomide, a thalidomide analog, was developed with the hope of improving both the efficacy and toxicity profile of thalidomide, and has subsequently shown significant clinical activity in patients with multiple myeloma. We describe the role of lenalidomide in patients with symptomatic multiple myeloma that is newly diagnosed, relapsed and/or refractory to other therapies, or concurrent with primary amyloidosis.
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PMID:Lenalidomide in multiple myeloma. 1807 Jul 15


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