Medication-related osteonecrosis of the jaw (MRONJ) is a severe complication of bisphosphonates (BPs) or other targeted agent therapies. MRONJ appears as exposed bone, pus, and swelling in the oral and maxillofacial regions. However, neither surgery nor conservative therapy can eliminate symptoms thoroughly. In addition to BPs, several antiresorptive and antiangiogenic agents, such as denosumab and bevacizumab, as well as targeted agents, such as sunitinib and temsirolimus, can cause osteonecrosis of  the  jaw according to the literature. This review aims to summarize the research progress on these new drugs.
Angiogenesis Inhibitors ; therapeutic use ; Bisphosphonate-Associated Osteonecrosis of the Jaw ; drug therapy ; Bone Density Conservation Agents ; adverse effects ; Denosumab ; therapeutic use ; Diphosphonates ; Humans

OBJECTIVE: Bevacizumab was recently approved by the US Food and Drug Administration for use in recurrent platinum resistant epithelial ovarian cancer (EOC), fallopian tube cancer (FTC), or primary peritoneal cancer (PPC) when no more than two prior cytotoxic regimens have been used; due to concerns for gastrointestinal perforation. We sought to determine bevacizumab-related toxicities in heavily pretreated recurrent EOC. METHODS: We performed a retrospective chart review of patients with recurrent EOC, FTC, and PPC from 2001 to 2011. Patients who received at least two prior chemotherapy regimens before bevacizumab were included. Medical records were reviewed for bevacizumab associated toxicities. The Wilcoxon-Mann-Whitney test was used to compare quantitative variables. Survival was estimated with the Kaplan-Meier method. RESULTS: Sixty patients met inclusion criteria. At the start of bevacizumab treatment, the median age was 60 years and the median body mass index was 26.5 kg/m². More than 50% of patients received bevacizumab after three prior cytotoxic regimens. Grade 3 or higher bevacizumab associated toxicity events occurred in four patients, including one patient who developed a rectovaginal fistula. The median overall survival from the start of bevacizumab treatment was 21.05 months (95% CI, 18.23 to 32.67; range, 1.9 to 110 months). The number of cytotoxic regimens prior to bevacizumab treatment did not differ in those that experienced a toxicity versus those that did not (p=0.66). CONCLUSION: The use of bevacizumab in heavily pretreated EOC, FTC, or PPC is worth consideration.
Adult ; Aged ; Aged, 80 and over ; Angiogenesis Inhibitors/*therapeutic use ; Bevacizumab/*adverse effects ; Fallopian Tube Neoplasms/*drug therapy ; Female ; Humans ; Intestinal Perforation/chemically induced ; Middle Aged ; Neoplasm Recurrence, Local/*drug therapy ; Neoplasms, Glandular and Epithelial/*drug therapy ; Ovarian Neoplasms/*drug therapy ; Peritoneal Neoplasms/*drug therapy ; Retrospective Studies

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

No abstract available.
Angiogenesis Inhibitors/*therapeutic use ; Bevacizumab/*therapeutic use ; Choroid/*blood supply ; Ciliary Arteries/pathology ; Fluorescein Angiography ; Humans ; Intravitreal Injections ; Ischemia/*drug therapy/etiology/physiopathology ; Male ; Meningeal Neoplasms/surgery ; Meningioma/surgery ; Neurosurgical Procedures/*adverse effects ; Retinal Detachment/*drug therapy/etiology/physiopathology ; Subretinal Fluid ; Vascular Endothelial Growth Factor A/antagonists & inhibitors ; Visual Acuity/physiology ; Young Adult

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 assess the efficacy and safety of bevacizumab (BEV) plus chemotherapeutic agents in the treatment of metastatic colorectal cancer (mCRC).

METHODSSeventy-seven mCRC patients received BEV plus 5-Fu type, oxaliplatin or irinotecan-based chemotherapy. The clinical efficacy and bevacizumab-related adverse reactions were observed. The efficacy assessment was conducted after at least 2 cycles of BEV therapy. The adverse reactions were recorded in each therapy cycle. Among the 77 cases, 64 patients had finished the efficacy assessment. The adverse reactions in all patients were assessed.

RESULTSThe overall response rate (ORR) of BEV plus chemotherapy regimen was 18.75% (12/64), and the disease control rate (DCR) was 75.0% (48/64). In 27 patients who received the regimen as first-line treatment, the ORR reached 37.0% (10/27), while the DCR was 85.2%. Four patients with potentially resectable lesions became resectable after the regimen and received R0 resection of the liver metastases successfully. Twenty-five patients who received the regimen as second line therapy had poor result with ORR 8.0% and DCR 76.0%. Hypertension was observed in 12 cases, with 8 cases of grade 1, 3 cases of grade 2, 1 case of grade 3. Various bleedings occurred in 24/77 cases (31.2%), all were of grade 1-2, including 17 cases of epistaxis, grade 1 hemorrhoid bleeding in one case, hematuria in 3 case (2 of grade 1, 1 of grade 2), GI bleeding in 2 cases, hemoptysis in 1 case (grade 2), and proteinuria in 4 cases (grade 1). Intestinal perforation occurred in 1 case (0.3%). In two patients who had incomplete intestinal obstruction history appeared exacerbated intestinal obstruction symptoms after the application of BEV plus CPT11 regimen.

CONCLUSIONSBEV plus chemotherapy regimen as first-line treatment can improve the ORR and DCR of mCRC patients. When it was used as second- or later-line therapy, it may display satisfied DCR, although with a poor efficacy. The bevacizumab-related toxicity is mild and can be well tolerated.

Adult ; Aged ; Angiogenesis Inhibitors ; adverse effects ; therapeutic use ; Antibodies, Monoclonal, Humanized ; adverse effects ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Bevacizumab ; Camptothecin ; adverse effects ; analogs & derivatives ; therapeutic use ; Colonic Neoplasms ; drug therapy ; pathology ; Deoxycytidine ; adverse effects ; analogs & derivatives ; therapeutic use ; Disease-Free Survival ; Female ; Fluorouracil ; adverse effects ; analogs & derivatives ; therapeutic use ; Follow-Up Studies ; Hemorrhage ; chemically induced ; Humans ; Hypertension ; chemically induced ; Leucovorin ; adverse effects ; therapeutic use ; Liver Neoplasms ; drug therapy ; secondary ; Lung Neoplasms ; drug therapy ; secondary ; Male ; Middle Aged ; Neoplasm Staging ; Organoplatinum Compounds ; adverse effects ; therapeutic use ; Proteinuria ; chemically induced ; Rectal Neoplasms ; drug therapy ; pathology ; Remission Induction ; Young Adult

This paper reports a case of pegylated interferon-associated retinopathy in a patient with chronic hepatitis C. A 32-year-old female with chronic hepatitis C undergoing pegylated interferon and ribavirin combination therapy complained of visual blurring. Features of interferon-associated retinopathy, including ocular complications such as cotton wool spots, retinal hemorrhages, macular edema, and branch retinal vein occlusion, were found in the fundus of both of her eyes. Pegylated interferon combination therapy was stopped, and the retinopathy of the patient was treated with intravitreal bevacizumab injections and panretinal photocoagulations. This case shows that pharmacokinetically improved pegylated interferon has ocular complications for patients with chronic hepatitis C. Accordingly, patients undergoing pegylated interferon treatment for hepatitis C need regular eye examinations for protection of their vision.
Adult ; Angiogenesis Inhibitors/therapeutic use ; Antibodies, Monoclonal, Humanized/therapeutic use ; Antiviral Agents/*adverse effects ; Female ; Hepatitis C, Chronic/*drug therapy ; Humans ; Interferon-alpha/*adverse effects ; Polyethylene Glycols/*adverse effects ; Recombinant Proteins/adverse effects ; Retinitis/*chemically induced/drug therapy ; Severity of Illness Index

The efficacy and safety of bevacizumab with modified irinotecan, leucovorin bolus, and 5-fluorouracil intravenous infusion (mIFL) in the first-line treatment of metastatic colorectal cancer (mCRC) has not been well evaluated in randomized clinical trials in Chinese patients. We conducted a phrase III trial in which patients with previously untreated mCRC were randomized 2:1 to the mIFL [irinotecan (125 mg/m(2)), leucovorin (20 mg/m(2)) bolus, and 5-fluorouracil intravenous infusion (500 mg/m(2)) weekly for four weeks every six weeks] plus bevacizumab (5 mg/kg every two weeks) group and the mIFL group, respectively. Co-primary objectives were progression-free survival (PFS) and 6-month PFS rate. In total, 214 patients were enrolled. Our results showed that addition of bevacizumab to mIFL significantly improved median PFS (4.2 months in the mIFL group vs. 8.3 months in the bevacizumab plus mIFL group, P < 0.001), 6-month PFS rate (25.0% vs. 62.6%, P < 0.001), median overall survival (13.4 months vs. 18.7 months, P = 0.014), and response rate (17% vs. 35%, P = 0.013). Grades 3 and 4 adverse events included diarrhea (21% in the mIFL group and 26% in the bevacizumab plus mIFL group) and neutropenia (19% in the mIFL group and 33% in the bevacizumab plus mIFL group). No wound-healing complications or congestive heart failure occurred. Our results suggested that bevacizumab plus mIFL is effective and well tolerated as first-line treatment for Chinese patients with mCRC. Clinical benefit and safety profiles were consistent with those observed in pivotal phase III trials with mainly Caucasian patients.
Adult ; Aged ; Angiogenesis Inhibitors ; adverse effects ; therapeutic use ; Antibodies, Monoclonal, Humanized ; adverse effects ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Asian Continental Ancestry Group ; Bevacizumab ; Camptothecin ; administration & dosage ; adverse effects ; analogs & derivatives ; Colorectal Neoplasms ; drug therapy ; pathology ; Diarrhea ; chemically induced ; Disease-Free Survival ; Female ; Fluorouracil ; administration & dosage ; adverse effects ; Humans ; Leucovorin ; administration & dosage ; adverse effects ; Male ; Middle Aged ; Neoplasm Metastasis ; Neutropenia ; chemically induced ; Prospective Studies ; Survival Rate ; Young Adult

OBJECTIVETo assess the efficacy and safety of bevacizumab plus irinotecan-based regimen for the first line treatment in metastatic colorectal cancer (mCRC) patients, and to investigate the correlation between serum tumor markers including CEA and CA19-9 and response as well as prognosis.

METHODSFrom May 2007 to July 2008, 67 previously untreated mCRC patients received treatment of IFL (n = 25), IFL plus Bevacizumab (n = 20) or FOLFIRI (n = 22). The treatment continued until disease progression or unacceptable toxicity. The data were retrospectively analyzed.

RESULTSAll patients were evaluable for response, survival and toxicity analysis. The objective response rate of IFL, IFL plus Bevacizumab or FOLFIRI regimen groups was 16.0% (4/25), 35.0% (7/20) and 18.2% (4/22), respectively (χ(2) = 6.026, P = 0.049). The median progression-free survival (PFS) of IFL plus bevacizumab group was 7.5 months, significantly improved as compared with 3.7 months in the IFL group and 4 months in FOLFIRI group (χ(2) = 11.97, P = 0.003). Of all 67 cases, the one-year survival rate was 47.0%, two-year survival rate was 27.0%, and the median overall survival (OS) was 13.0 months, with no significant difference among the three treatment groups (χ(2) = 3.42, P = 0.18). The serum CEA and CA19-9 levels were decreased after treatment, but with no significant difference among the three groups (P > 0.05). The common toxicity profiles of IFL and FOLFIRI regimens were diarrhea and neutropenia, while the toxicity related to bevacizumab was consistent with that documented in previous literature, such as hypertension, hemorrhage, cardiac toxicity and delayed wound healing.

CONCLUSIONThe addition of bevacizumab to irinotecan-based regimen significantly improves the response rate and PFS in first-line treatment for patients with mCRC and its toxicity is well tolerated.

Adenocarcinoma ; blood ; drug therapy ; secondary ; Adenocarcinoma, Mucinous ; blood ; drug therapy ; secondary ; Adult ; Aged ; Angiogenesis Inhibitors ; adverse effects ; therapeutic use ; Antibodies, Monoclonal, Humanized ; adverse effects ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Bevacizumab ; CA-19-9 Antigen ; blood ; Camptothecin ; administration & dosage ; analogs & derivatives ; therapeutic use ; Carcinoembryonic Antigen ; blood ; Colonic Neoplasms ; blood ; drug therapy ; secondary ; Diarrhea ; chemically induced ; Disease-Free Survival ; Female ; Fluorouracil ; administration & dosage ; therapeutic use ; Follow-Up Studies ; Humans ; Hypertension ; chemically induced ; Leucovorin ; therapeutic use ; Male ; Middle Aged ; Neutropenia ; chemically induced ; Rectal Neoplasms ; blood ; drug therapy ; secondary ; Remission Induction ; Retrospective Studies ; Survival Rate ; Young Adult

BACKGROUNDbevacizumab is a humanized recombinant vascular endothelial growth factor (VEGF) monoclonal antibody, which specifically binds to VEGF and inhibits tumor cell growth, proliferation and metastasis. We aimed to investigate the safety and pharmacokinetics of bevacizumab in Chinese patients with advanced cancer.

METHODSThirty-nine Chinese patients with metastatic or relapsed cancers who failed prior therapy were enrolled in this phase I study of bevacizumab. Bevacizumab was infused by a calculated pump at doses from 5 mg/kg to 15 mg/kg in 90 minutes. Patients underwent serial pharmacokinetic evaluations. Patients that received at least one infusion of bevacizumab were included in the safety study.

RESULTSThirty-five patients finished all 5 infusions following protocol. One patient withdrew after 3 infusions due to grade 3 proteinuria. Common adverse events possibly related to the study drug were proteinuria (17/39, 43.6%), hypertension (13/39, 33.3%), gingival bleeding (7/39, 17.9%), epistaxis (6/39, 15.4%), pharyngeal inflammation (6/39, 15.4%), fatigue (6/39, 15.4%) and stomatitis (4/39, 10.3%). Bevacizumab pharmacokinetics was linear within the range of 5 mg/kg q2w--10 mg/kg q2w and 15 mg/kg q3w. CL (clearance), Vd (volume of distribution at elimination) and Vss (volume of distribution at steady state) were similar after single and multiple doses at 5, 10 and 15 mg/kg.

CONCLUSIONSBevacizumab is well tolerated in Chinese patients. No unexpected adverse events were observed. There is no racial difference in the pharmacokinetics.

Adult ; Aged ; Angiogenesis Inhibitors ; adverse effects ; pharmacokinetics ; therapeutic use ; Antibodies, Monoclonal ; adverse effects ; pharmacokinetics ; therapeutic use ; Antibodies, Monoclonal, Humanized ; Asian Continental Ancestry Group ; Bevacizumab ; Female ; Humans ; Male ; Middle Aged ; Neoplasms ; drug therapy