Idiopathic myelofibrosis a Philadelphia-negative chronic myeloproliferative disorder. Potentially curative therapies, such as stem-cell transplantation, are reserved only for a minority of patients. Currently palliative therapies such as androgen and hydroxycarbamide are commonly used but with poor results. Thalidomide has anti-angiogenic effect and also can inhibit cytokines, and therefore plays a certain role in the treatment of a subset of idiopathic myelofibrosis.
Angiogenesis Inhibitors ; adverse effects ; therapeutic use ; Humans ; Immunosuppressive Agents ; adverse effects ; therapeutic use ; Primary Myelofibrosis ; drug therapy ; Thalidomide ; adverse effects ; therapeutic use ; Treatment Outcome

BACKGROUNDLenalidomide has emerged as an important treatment for patients with multiple myeloma (MM). However, its role in the management of MM is still controversial and requires further clarification. The aim of this study was to evaluate efficacy and safety of lenalidomide for MM using a meta-analysis.

METHODSWe searched the electronic databases including: PubMed, EMBASE and the Cochrane Center Register of Controlled Trials. Seven randomized clinical trials were identified, which included a total of 2357 patients with MM who received lenalidomide-containing, noncontaining lenalidomide regimens or placebo as induction therapy or maintenance therapy. The outcomes included overall response (OR) rate, complete response (CR) rate, 3-year progression-free survival (PFS) rate, 3-year overall survival (OS) rate, and different types of treatment-related adverse events. We calculated the risk ratios (RRs) as well as their 95% confidence intervals of these outcomes and pooled the results using RevMan 5.2 software.

RESULTSFor patients with previously untreated MM, OR rate and CR rate was significantly higher in lenalidomide-containing group than the control group. For relapsed or refractory MM patients, lenalidomide-containing regimens significantly improved the OR rate, CR rate, 3-year PFS rate and 3-year OS rate. With regard to MM patients after autologous stem cell transplantation, lenalidomide maintenance therapy significantly improved 3-year PFS rate but did not result in improved 3-year OS rate. In terms of toxicities, lenalidomide therapy has a higher rate of Grade 3-4 grade cytopenias, infection, deep-vein thrombosis, and diarrhea. Furthermore, the incidence of second primary malignancies was significantly higher in the lenalidomide group.

CONCLUSIONSThe lenalidomide-containing regimens as induction therapy clearly increased response rates and improved intervals of survival with acceptable toxicity rates for patients with MM. However, when physicians choose to use the lenalidomide as maintenance therapy, whether the benefits outweigh the risks should be taken into account.

Angiogenesis Inhibitors ; adverse effects ; therapeutic use ; Humans ; Multiple Myeloma ; drug therapy ; Randomized Controlled Trials as Topic ; Thalidomide ; adverse effects ; analogs & derivatives ; therapeutic use ; Treatment Outcome

Bortezomib, an inhibitor of 26S proteosome, is recently approved treatment option for multiple myeloma. Thalidomide, a drug with immunomodulating and antiangiogenic effects, has also shown promise as an effective treatment in multiple myeloma. Pulmonary complications are believed to be rare, especially interstitial lung disease. Here, we describe a patient with dyspnea and diffuse pulmonary infiltrates while receiving bortezomib and thalidomide in combination with dexamethasone for treatment-naive multiple myeloma. Bronchoalveolar lavage demonstrated a significant decrease in the ratio of CD4 : CD8 T lymphocytes (CD4/8 ratio, 0.54). Extensive workup for other causes, including infections, was negative. A lung biopsy under video-assisted thorascopic surgery revealed a diagnosis of nonspecific interstitial pneumonitis. The symptoms and imaging study findings improved after initiating steroid treatment. Physicians should be aware of this potential complication in patients receiving the novel molecular-targeted antineoplastic agents, bortezomib and thalidomide, who present with dyspnea and new pulmonary infiltrates and fail to improve despite treatment with broad-spectrum antibiotics.
Aged ; Boronic Acids/*adverse effects/therapeutic use ; Dexamethasone/therapeutic use ; Humans ; Lung Diseases, Interstitial/*chemically induced ; Male ; Multiple Myeloma/*drug therapy ; Pyrazines/*adverse effects/therapeutic use ; Thalidomide/*adverse effects/therapeutic use

A 63-year-old female diagnosed with relapsed multiple myeloma visited our hospital complaining of a persistent cough. Since July 2006, she had been taking 100 mg thalidomide daily and gradually developed shortness of breath and a persistent dry cough. A chest X-ray and computed tomography showed ground glass opacities in both lungs. An open lung biopsy of the right middle lobe under general anesthesia revealed chronic peribronchial inflammation, mild interstitial fibrosis, and intra-alveolar macrophage infiltration, with some hemosiderin features, compatible with non-specific interstitial pneumonia (NSIP). After discontinuing the thalidomide, the patient's symptoms did not deteriorate, although the radiographs did not improve. The patient is alive and well with regular outpatient follow-up without progression of the NSIP.
Female ; Humans ; Lung Diseases, Interstitial/*chemically induced ; Middle Aged ; Multiple Myeloma/*drug therapy ; Thalidomide/*adverse effects/therapeutic use

In recent years, the incidence of chronic lymphocytic leukemia (CLL) is increasing. Microenvironment and immune system play a key role in the pathogenesis of CLL. The immune system is aggravated by the use of chemotherapeutic agents, such as fludarabine and cyclophosphamide with rituximab(FCR) which are the current standards in frontline therapy. This leads to an increase of infection incidence in patients, resulting in a poor prognosis. The present situation was changed by lenalidomide. Recent studies indicated that lenalidomide monotherapy in treatment of refractory or relapsed CLL patients, the overall response rate(ORR) reached about 32%-47%, CR roughly was 7%-13%; when lenalidomide and rituximab were combined for treatment of refractory or relapsed CLL patients, the ORR reached about 53%-66%, CR about 12%-13%. Moreover, when lenalidomide and ofatumumab were combined, the efficacy is improved significantly and the adverse reactions are greatly reduced. The adverse reactions are neutrophilic granulocytopenia, thrombocytopenia, anemia, tumor lysis syndrome(TLS), tumor flare reaction(TFR) and venous thromboembolism(VTE). This review focuses on the related studies and the latest progress about lenalidomide in CLL.
Angiogenesis Inhibitors ; adverse effects ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell ; drug therapy ; Thalidomide ; adverse effects ; analogs & derivatives ; therapeutic use

OBJECTIVETo analyse the efficacy and safety of thalidomide (Thal) for patients with multiple myeloma (MM).

METHODSEffectiveness and adverse events of 102 MM patients treated with thalidomide at a median dosage of 200 mg/d. Thirteen cases were treated with Thal alone (group A), and 105 case with Thal in combination with other therapeutic agents (group B) were retrospectively analyzed.

RESULT1) The response rate (RR) (CR + PR) was 65.4% for induction therapy in 52 cases and 45.5% for salvage therapy in 66 cases. RR in group B was higher than that in group A (58.1% versus 23.1/%, P= 0.017), and the non-response/progress (NR) rate was lower (15.2% versus 46.2%, P= 0.015). In group B, the NR rate was lower in 50 cases of newly diagnosed MM than in 55 cases of refractory or relapsed MM (6.0% versus 23.6%, P=0.012). In group B, RR between Thal+VAD or M, regimen (72 cases) and Thal + MP regimen (33 cases) was not statistically significant (62.5% versus 48.5%, P >0.05). 2) The median duration of response maintenance was 15.5 (1.0-58.0) months in 21 cases. 3) Among 97 patients with follow-up data, the estimated median duration of OS was 44 months in a median follow-up duration of 20 months and the accumulative time for use of Thal was 8 months. In univariate analysis,the accumulative duration for use of Thal 6 months, hemoglobin > or = 100 g/L and bone marrow megakaryocytes > 20 per smear were associated with longer OS (P = 0.0014, 0.0101, 0.019, respectively). 4) Multivariate analysis suggested that the accumulative time for use of Thal and bone marrow megakaryocytes > 20 were independent good prognostic factors for OS (P = 0.006, 0.036, respectively). 5) The adverse events of Thal were mostly endurable, the rate of thrombus events was lower than that reported in literature.

CONCLUSIONThalidomide alone or combined with chemotherapy is an useful therapy for MM. The accumulative time for use longer than 6 months may improve survival.

Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Multiple Myeloma ; drug therapy ; Prognosis ; Retrospective Studies ; Thalidomide ; adverse effects ; therapeutic use ; Treatment Outcome

Adult ; Aged ; Anticoagulants ; therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Phytotherapy ; Salvia miltiorrhiza ; Thalidomide ; adverse effects ; Venous Thromboembolism ; chemically induced ; prevention & control

OBJECTIVEThis study investigates the efficacy and tolerability of capecitabine plus thalidomide in patients with advanced pancreatic cancer who previously underwent gemcitabine-based therapy.

METHODSSixty-one patients with unresectable or metastatic PC who had progressed on single-agent Gem or a Gem-containing regimen were enrolled. The patients were randomly divided into two groups. One group (31 patients) was treated with capecitabine alone, and another group was treated with capecitabine plus thalidomide. Capecitabine was administered orally twice a day at a dose of 1, 250 mg/m(2) for 14-day followed by 7-day rest and oral thalidomide 100 mg was given daily without interruption until disease progression or occurrence of unacceptable toxicity.

RESULTSThe PFS was 2.8 months (95%CI 2.4 - 3.2) vs. 3.1 months (95%CI 2.6-3.6, P < 0.05) and the OS was 6.1 months (95%CI 5.3 - 6.9) vs. 6.3 months (95%CI 5.2 - 7.4, P = 0.426). In the capecitabine alone group, one patient experienced a partial response (PR), 10 patients showed stable disease (SD) and 20 patients had progressive disease (PD). The another group, two patients experienced a partial response (PR), 11 patients SD, and 17 patients PD. The disease control rates were 35.5% and 43.3%, respectively. The major adverse reaction in the two groups was grade 3 diarrhea.

CONCLUSIONCapecitabine plus thalidomide regimen is marginally effective and well tolerated in the second-line setting in patients with gemcitabine-refractory advanced pancreatic cancer.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Capecitabine ; Deoxycytidine ; administration & dosage ; adverse effects ; analogs & derivatives ; Diarrhea ; chemically induced ; Disease-Free Survival ; Female ; Fluorouracil ; administration & dosage ; adverse effects ; analogs & derivatives ; Follow-Up Studies ; Humans ; Leukopenia ; chemically induced ; Male ; Middle Aged ; Neoplasm Staging ; Pancreatic Neoplasms ; drug therapy ; pathology ; Remission Induction ; Survival Rate ; Thalidomide ; administration & dosage ; adverse effects

OBJECTIVETo observe the effect of thalidomide in preventing nausea and vomiting induced by emetogenic cisplatin (CDDP) chemotherapy in patients with advanced non-small cell lung cancer.

METHODSThis study was carried out as a prospective, randomized control clinical trial. 61 patients with advanced non-small cell lung cancer were scheduled to receive chemotherapy (gemcitabin 1000 mg/m(2) i.v. gtt d1, 8 and CDDP 75 mg/m(2) i.v. gtt d1, GP regimen). The patients were randomly divided into a treatment and control groups. All patients in both groups received ramosetron 0.3 mg intravenously (i.v.) and metoclopramide 20 mg intramuscularly (i.m.) 30 min prior to chemotherapy to prevent nausea and emesis on day 1. In the treatment group, addition of thalidomide (50 mg p.o. bid) were administered on days 1 to 5 after the start of chemotherapy.

RESULTSAcute nausea was effectively controlled in 74.2% of the patients in the control group and in 90.0% of treatment group. Acute vomiting was effectively controlled in 90.3% of the patients in the control group and in 93.3% of treatment group. No statistically significant differences showed in effective control of acute nausea and vomiting between the 2 groups (P = 0.108; P = 1.000). Delayed nausea was effectively controlled in 19.4% of the patients in control group and in 56.7% in the treatment group. Delayed vomiting was effectively controlled in 48.4% of the patients in control group and 76.7% in treatment group. Statistically there was a significant differences in effective control of delayed nausea and vomiting between the 2 groups (P = 0.003, P = 0.023). Both antiemetic regimens were well tolerated, and no significant difference was observed in adverse events between the 2 groups (P > 0.05).

CONCLUSIONOur results demonstrate that thalidomide is highly effective in controlling delayed nausea and vomiting episodes in patients induced by moderately emetogenic chemotherapy. Moreover, no serious toxic effects are induced by this treatment.

Antiemetics ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; pathology ; Cisplatin ; administration & dosage ; Deoxycytidine ; administration & dosage ; analogs & derivatives ; Female ; Humans ; Lung Neoplasms ; drug therapy ; pathology ; Male ; Middle Aged ; Nausea ; chemically induced ; prevention & control ; Neoplasm Staging ; Prospective Studies ; Thalidomide ; therapeutic use ; Vomiting ; chemically induced ; prevention & control

OBJECTIVETo observe the effective mechanism and side effects of thalidomide to multiple myeloma (MM).

METHODSTen cases of MM were studied, of which 3 were previously untreated and 7 refractory or relapsed. Bone marrow microvascular density (MVD) was detected by factor-VIII related antigen and CD(34) immunohistological staining and serum concentration of vascular endothelial growth factor (VEGF) before and after treatment was determined by ELISA. The initial dosage of thalidomide was 100 approximately 200 mg/d with a weekly escalation of 50 mg/d to 450 approximately 650 mg/d. The therapeutic effectiveness is classified into partial remission, improvement and uneffective according to the decrease of serum M protein and bone marrow myeloma cells. Anemia, renal function and blood electrolytes were also observed.

RESULTSBefore treatment, MVD was 73.32 +/- 28.80 and 32.30 +/- 12.50 in MM and control group, respectively, (P < 0.01). MVD in MM group decreased to 56.12 +/- 19.34 after treatment, and was of significant difference (P < 0.05) as compared to the pretreatment value. However, there was still a significant difference as compared to control (56.12 +/- 19.34 vs 32.30 +/- 12.50, P < 0.01). The concentration of VEGF significantly decreased after treatment [from (178.23 +/- 26.56) ng/L to (78.48 +/- 19.98) ng/L, P < 0.01)]. The total effective rate was 70%. There were no serious side effects.

CONCLUSIONMVD and VEGF concentration were decreased obviously by thalidomide treatment. The dosage of 450 approximately 650 mg/d might be effective in refractory or initial MM.

Aged ; Angiogenesis Inhibitors ; adverse effects ; therapeutic use ; Antigens, CD34 ; analysis ; Bone Marrow ; blood supply ; drug effects ; Constipation ; chemically induced ; Endothelial Growth Factors ; blood ; Fatigue ; chemically induced ; Female ; Humans ; Immunohistochemistry ; Intercellular Signaling Peptides and Proteins ; blood ; Lymphokines ; blood ; drug effects ; Male ; Middle Aged ; Multiple Myeloma ; blood ; drug therapy ; pathology ; Nausea ; chemically induced ; Sleep Wake Disorders ; chemically induced ; Thalidomide ; adverse effects ; therapeutic use ; Treatment Outcome ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors ; von Willebrand Factor ; analysis