BACKGROUNDNasopharyngeal carcinoma (NPC) is a squamous-cell carcinoma especially prevailing among the natives of southern China. The regimen of concurrent chemoradiotherapy (CCRT) that include platinum and 5-fluorouracil (5-FU) is considered to be the standard treatment for NPC. However, its clinical use is limited by its toxicity. Our purpose was to evaluate the efficacy and safety of the regimen of CCRT with taxanes and platinum versus the regimen of CCRT with 5-FU and platinum in NPC treatment.

METHODSMedline, the Cochrane library, and the Chinese medical literature database were searched for eligible studies. Meta-analysis was performed using Review Manager (Version 5.2).

RESULTSSix random controlled trials (RCTs) including 514 patients met our criteria. Meta-analysis showed that the regimen of CCRT with taxanes and platinum had an improved significant difference in complete remission (CR) and less incidence rate in adverse reactions such as gastrointestinal impairment grades III-IV, liver and kidney impairment grades I-II, and radiodermatitis grades III-IV versus the conventional regimen of CCRT with 5-FU and platinum, while the longterm effectiveness rate of overall survival, locoregional failure-free survival, or distant metastasis failure-free survival between the two groups was therapeutic equivalence.

CONCLUSIONSThe regimen of CCRT with taxanes and platinum in NPC therapy may be more efficient and safe compared to the conventional modality of 5-FU and platinum in CCRT. However, we need more high-quality studies of multi-center and randomized double-blind clinical trials to further compare, analyze, and confirm the findings.

Carcinoma ; Chemoradiotherapy ; Fluorouracil ; administration & dosage ; therapeutic use ; Humans ; Nasopharyngeal Neoplasms ; drug therapy ; Platinum ; administration & dosage ; therapeutic use ; Taxoids ; administration & dosage ; therapeutic use ; Treatment Outcome

BACKGROUND: Taxanes are an essential class of antineoplastic agents used to treat various cancers and are a fundamental cause of hypersensitivity reactions. In addition, other adverse events, such as bone marrow toxicity and peripheral neuropathy, can lead to chemotherapy discontinuation. This study aimed to evaluate the safety of taxanes in the real world. METHODS: Taxane-associated adverse events were identified by the Medical Dictionary for Regulatory Activities Preferred Terms and analyzed and compared by mining the US Food and Drug Administration Adverse Event Reporting System pharmacovigilance database from January 2004 to December 2019. Reported adverse events, such as hypersensitivity reaction, bone marrow toxicity, and peripheral neuropathy, were analyzed with the following signal detection algorithms: reporting odds ratio (ROR), proportional reporting ratio (PRR), multi-item gamma Poisson shrinker (MGPS), Bayesian confidence propagation neural network (BCPNN), and logistic regression methods. Adverse outcome events and death outcome rates were compared between different taxane groups using Pearson's χ2 test, whereas significance was determined at P < 0.05 with a 95% confidence interval (CI). RESULTS: A total of 966 reports of hypersensitivity reactions, 1109 reports of bone marrow toxicity, and 1374 reports of peripheral neuropathy were analyzed. Compared with paclitaxel and docetaxel, bone marrow toxicity following the use of nab-paclitaxel had the highest ROR of 6.45 (95% two-sided CI, 6.05-6.88), PRR of 5.66, (χ2 = 4342.98), information component of 2.50 (95% one-sided CI = 2.34), and empirical Bayes geometric mean of 5.64 (95% one-sided CI = 5.34). Peripheral neuropathy following the use of nab-paclitaxel showed a higher ROR of 12.78 (95% two-sided CI, 11.55-14.14), PRR of 12.16 (χ2 = 4060.88), information component of 3.59 (95% one-sided CI = 3.25), and empirical Bayes geometric mean of 12.07 (95% one-sided CI = 11.09). CONCLUSIONS The results showed that bone marrow toxicity and peripheral neuropathy were the major adverse events induced by taxanes. Nab-paclitaxel exhibited the highest potential for taxane-associated adverse events. Further research in the future is warranted to explain taxane-associated adverse effects in real-world circumstances.
Adverse Drug Reaction Reporting Systems ; Bayes Theorem ; Bridged-Ring Compounds ; Taxoids/adverse effects* ; United States ; United States Food and Drug Administration

OBJECTIVETo investigate the proliferation inhibition and apoptosis-inducing effect of docetaxel-loaded lipid microbubble (DLLM) combined with ultrasound targeted microbubble destruction (UTMD) on human pancreatic cancer cells in vitro.

METHODSDLLM was prepared by mechanical vibration, and its physical properties were characterized. The median inhibitory concentration (IC(50)) of DLLM was determined with MTT assay, and its cytotoxicity evaluated with cell counting Kit-8 (CCK-8) assay. The effects of docetaxel, DLLM, and DLLM combined with UTMD on cell cycle and apoptosis of BxPC3 cells were tested with flow cytometry (FCM) and TUNEL assay, respectively.

RESULTSDLLM had an average size of 1.6 µm, and the average drug entrapment efficiency and drug-loaded amount was 64.2% and 16.1%, respectively. Compared with the control groups, DLLM had a significantly enhanced cytotoxic effect (P<0.01) and caused an increased apoptosis rate in BxPC3 cells (P<0.01). Cell cycle analysis showed that DLLM combined with UTMD resulted in an significantly higher percentage of cells with G(2)/M phase arrest than the other treatments (P<0.01).

CONCLUSIONSDLLM combined with UTMD can increase G(2)/M phase arrest and enhance the proliferation inhibition and apoptosis-inducing effect on BxPC3 cells, and can serve as an effective drug delivery system for pancreatic cancer therapy.

Apoptosis ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Drug Carriers ; administration & dosage ; pharmacology ; Humans ; Microbubbles ; Pancreatic Neoplasms ; pathology ; Taxoids ; administration & dosage ; pharmacology

BACKGROUNDA phase III trial involving docetaxel, cisplatin, and fluorouracil (DCF) in the treatment of advanced gastric cancer was shown to have superior efficacy compared to cisplatin and fluorouracil alone, but with a high rate of hematologic toxicity. To reduce toxicity while maintaining the efficacy of DCF, we reduced the doses of docetaxel (D) and cis-platinum (CDDP), and administered 5-fluorouracil (5-FU) via a continuous intravenous (CIV) infusion.

METHODSChemotherapy-naive patients with gastric adenocarcinomas received D (60 mg/m(2) 1 hour on day 1), CDDP (30 mg/m(2) on days 1 and 2), and 5-FU (1500 mg×m(-2)×24 h(-1) CIV on days 1 and 8 every 3 weeks). The primary endpoint was the response rate.

RESULTSFourteen patients were enrolled. Based on the efficacy evaluation following at least 2 cycles of treatment, there was 7.1% complete remission (CR), 71% partial remission (PR), 14% stable disease (NC/SD), and 7.1% progressive disease (PD). The median survival time was 13 months. Nine patients (64%) had grade III-IV neutropenia, and 4 patients (29%) had grade IV neutropenia, among whom 1 had grade IV neutropenia with grade III nausea and vomiting.

CONCLUSIONThe modified DCF regimen is highly active and has a favorable toxicity profile in Chinese patients with gastric cancer.

Adenocarcinoma ; drug therapy ; Antimetabolites, Antineoplastic ; administration & dosage ; Antineoplastic Agents ; administration & dosage ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Cisplatin ; administration & dosage ; Female ; Fluorouracil ; administration & dosage ; Humans ; Male ; Middle Aged ; Stomach Neoplasms ; drug therapy ; Taxoids ; administration & dosage

OBJECTIVETo compare the therapeutic effects, toxic side effects and influence on the immune function in patients treated with TPF [docetaxel (DOC) + cisplatin (DDP) + 5-fluorouracil (5-Fu)] induction chronochemotherapy and conventional chemotherapy for locally advanced nasopharyngeal (NPC).

METHODSSeventy patients with locally advanced nasopharyngeal carcinoma were treated in our department at their first visit from April 2013 to December 2013. They were divided randomly into two groups: the chronochemotherapy group (38 patients) and conventional chemotherapy group (32 patients). All of the patients were treated with TPF regimen with 2 cycles of induction chemotherapy in a 21-28-days/cycle. The chronochemotherapy group: DOC: 75 mg/m2, i. v. gtt, d1 (03: 30-04: 30); DDP: 75 mg/m2, 10 am-10 pm, c.i.v, d1-d5; 5-Fu: 750 mg·m(-2)·d(-1), 10 pm-10 am, c. i.v., d1-d5, both chemotherapies were administered by intravenous infusion using an automatic electric pump. The conventional chemotherapy group: Both DOC and DDP were administered intravenously at a dose of 75 mg/m2 on d1. 5-Fu was given at a dose of 750 mg/m2 for 24 hours from d1-d5 with continuous infusion in a total of 120 hours. In this procedure, prescribing the conventional intravenous infusion, intensity modulated radiation therapy was used after the induction chemotherapy. The prescribed nasopharyngeal lesion dose (GTVnx) was 69.96 Gy/33 fractions for the T1-T2 nasopharygeal cancer, while 73.92 Gy/33 fractions nasopharynx lesion dose (GTVnx) for the T3-T4 nasopharyngeal cancer. The planning target volume (PTV) of positive lymph node (PTVnd) dose was 69.96 Gy/33 fractions. Concurrent chemoradiotherapy: cisplatin 100 mg/m2, i. v. gtt. d1-d2, and there were two cycles in total and 21 days each cycle.

RESULTSSixty-six patients were evaluable for the response assessment. There were 36 patients in the chronochemotherapy group and 30 patients in the conventional chemotherapy group. After the induction chemotherapy, no CR case was found in both of the two groups. The PR was 80.6% in the chronochemotherapy group and 50.0% in the conventional chemotherapy group (P=0.009). After concurrent chemoradiotherapy, the CR rate in the chronocheotherapy group was 45.5%, significantly higher than 20.7% in the conventional chemotherapy group (P=0.040). Secondly, the incidence rates of adverse reactions including bone marrow suppression, nausea, vomiting, diarrhea, constipation, oral mucositis, fatigue, anorexia in the chrono-chemotherapy group were significantly lower than that in the conventional group (P<0.05 for all). Finally, compared the two groups, the CD4+ /CD8+ ratio was significantly lower in the chronochemotherapy group than that in the conventional chemotherapy group (P<0.05). The lymphocytes CD19+ and CD4+/CD8+ were decreased and CD3+, CD4+, CD8+, CD16++CD56+ were increased in the chronochemotherapy group, while only CD3+ and CD8+ were increased in the conventional chemotherapy group.

CONCLUSIONSCompared with the conventional chemotherapy, the chronochemotherapy may be more favorable in the treatment of NPC, with a better therapeutic effects and effectiveness than that of conventional chemotherapy after induction chemotherapy, with less side effects, and can improve the immune function in the patients.

Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; Carcinoma ; Chemoradiotherapy ; Cisplatin ; administration & dosage ; Drug Chronotherapy ; Fluorouracil ; administration & dosage ; Humans ; Induction Chemotherapy ; methods ; Nasopharyngeal Neoplasms ; drug therapy ; pathology ; radiotherapy ; Nausea ; Neoplasm Staging ; Radiotherapy, Intensity-Modulated ; Taxoids ; administration & dosage ; Treatment Outcome

OBJECTIVETo compare docetaxel plus prednisone with mitoxantrone plus prednisone as first-line chemotherapy for metastatic hormone-refractory prostate cancer (mHRPC).

METHODSFrom January 2007 through August 2010, 62 patients with mHRPC received 5 mg of prednisone twice daily were randomly assigned to receive mitoxantrone 12 mg/m² every three weeks (group A) or 75 mg/m² every three weeks (group B). The cycles of each regimen were less than 10 times. The primary end point was overall survival. The secondary end points were the prostate-specific antigen (PSA) response rate, the duration of PSA response and the objective tumor response rate (ORR). All the t test, χ² test and Fisher's exact test were performed between 2 groups.

RESULTSThirty-one patients enrolled in group A received a median 4 cycles of regimen (range 1 - 10), whereas 30 patients enrolled in group B received a median of 7 cycles of regimen (range 2 - 10). There were 45.2% patients in group A and 70.0% in group B had PSA response (χ² = 3.85, P < 0.05). The duration time of PSA response was 121 days (range 20-323 days) in group A and 168 days (range 42 - 447 days) in group B, respectively. The ORR was 15.0(3/20) in group A and 10.3% (3/29) in group B, respectively. The median survival was 511 days (95%CI: 357 - 665 days) in group A and 833 days (95%CI: 634 - 1032 days) in group B, respectively (χ² = 4.20, P = 0.040). The incidence of thrombocytopenia in group A was higher than group B (χ² = 5.60, P = 0.018); the incidences of nausea and vomiting (χ² = 4.32, P = 0.038), diarrhea (P = 0.024), fatigue (χ² = 5.90, P = 0.015), and alopecia (χ² = 5.42, P = 0.020) in group B were higher than group A.

CONCLUSIONDocetaxel plus prednisone can lead to superior overall survival and PSA response rate in patients with mHRPC.

Aged ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; therapeutic use ; Humans ; Male ; Middle Aged ; Mitoxantrone ; administration & dosage ; Neoplasm Metastasis ; Prednisone ; administration & dosage ; Prospective Studies ; Prostatic Neoplasms, Castration-Resistant ; drug therapy ; secondary ; Taxoids ; administration & dosage ; Treatment Outcome

Anthracyclines ; pharmacology ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Breast Neoplasms ; drug therapy ; metabolism ; Cisplatin ; administration & dosage ; Deoxycytidine ; administration & dosage ; analogs & derivatives ; Drug Resistance, Neoplasm ; Female ; Humans ; Taxoids ; administration & dosage ; Vinblastine ; administration & dosage ; analogs & derivatives

BACKGROUND/AIMS: To describe the toxicity profile of anti-neoplastic agents from real clinical settings, we analyzed spontaneously reported adverse events (AEs) using data from the adverse drug reaction (ADR) reporting system of the Korean Food and Drug Administration (KFDA). METHODS: Data were extracted from the nationwide spontaneous ADR reporting system of KFDA from July 2009 to December 2010. We extracted and analyzed data related to chemotherapy and identified unlabeled ADR that were not described in the package insert of the products. RESULTS: In total, 5,867 cases of antineoplastic agent-related AE reports were identified after excluding cases for duplication and cases assessed as 'unlikely' and 'unclassifiable', based on expert opinion. Of the patients with AEs, 52.4% were males and the median age was 56 years. In total, 460 AEs (7.8%) from 267 patients were reported as 'serious' AEs. The most common causative anti-cancer drug class was pyrimidine analogs (31.5%), followed by platinum compounds (19.9%), protein kinase inhibitors (10.8%), and taxanes (8.8%). The most common clinical manifestation of AEs was gastrointestinal toxicities (25.5%), followed by skin disorders (25.3%), and generalized reactions (14.3%). In total, 168 cases (2.9%) of unlabeled AEs were identified. Among these, 10 were reported as serious AEs. CONCLUSIONS: The most common causative class of antineoplastic agents was that of pyrimidine analogs. Gastrointestinal and dermatological toxicities were the most common clinical chemotherapy-related adverse events. Further investigation and monitoring to evaluate causality associated with unlabeled AEs identified in this analysis are needed.
Antineoplastic Agents ; Drug Toxicity ; Expert Testimony ; Humans ; Male ; Pharmacovigilance ; Platinum Compounds ; Product Labeling ; Protein Kinase Inhibitors ; Pyrimidines ; Skin ; Statistics as Topic ; Taxoids ; United States Food and Drug Administration

BACKGROUND/AIMS: To describe the toxicity profile of anti-neoplastic agents from real clinical settings, we analyzed spontaneously reported adverse events (AEs) using data from the adverse drug reaction (ADR) reporting system of the Korean Food and Drug Administration (KFDA). METHODS: Data were extracted from the nationwide spontaneous ADR reporting system of KFDA from July 2009 to December 2010. We extracted and analyzed data related to chemotherapy and identified unlabeled ADR that were not described in the package insert of the products. RESULTS: In total, 5,867 cases of antineoplastic agent-related AE reports were identified after excluding cases for duplication and cases assessed as 'unlikely' and 'unclassifiable', based on expert opinion. Of the patients with AEs, 52.4% were males and the median age was 56 years. In total, 460 AEs (7.8%) from 267 patients were reported as 'serious' AEs. The most common causative anti-cancer drug class was pyrimidine analogs (31.5%), followed by platinum compounds (19.9%), protein kinase inhibitors (10.8%), and taxanes (8.8%). The most common clinical manifestation of AEs was gastrointestinal toxicities (25.5%), followed by skin disorders (25.3%), and generalized reactions (14.3%). In total, 168 cases (2.9%) of unlabeled AEs were identified. Among these, 10 were reported as serious AEs. CONCLUSIONS: The most common causative class of antineoplastic agents was that of pyrimidine analogs. Gastrointestinal and dermatological toxicities were the most common clinical chemotherapy-related adverse events. Further investigation and monitoring to evaluate causality associated with unlabeled AEs identified in this analysis are needed.
Antineoplastic Agents ; Drug Toxicity ; Expert Testimony ; Humans ; Male ; Pharmacovigilance ; Platinum Compounds ; Product Labeling ; Protein Kinase Inhibitors ; Pyrimidines ; Skin ; Statistics as Topic ; Taxoids ; United States Food and Drug Administration

Prostate cancer is the most common cancer in men in United States and the fifth most common cancer in men in Korea. Although the majority of patients with metastatic prostate cancer initially respond to androgen deprivation therapy, almost all patients will eventually progress to develop castration-resistant prostate cancer (CRPC). Treatment options for CRPC remain limited. Prostate cancer was considered unresponsive to chemotherapy until the mid-1990s, when mitoxantrone combined with prednisone was shown to play a role in the palliative treatment of patients with CRPC. In 2004, two large randomized clinical trials demonstrated for the first time a small but significant survival advantage of docetaxel-based chemotherapy compared with mitoxantrone in patients with metastatic CRPC. Recently, cabazitaxel was shown to improve survival in patients with metastatic CRPC who progressed after docetaxel-based chemotherapy. Sipuleucel-T was also demonstrated to improve overall survival in patients with asymptomatic or minimally symptomatic metastatic CRPC. Along with mitoxantrone and docetaxel, cabazitaxel and sipuleucel-T are now approved for use in metastatic CRPC by the US Food and Drug Administration. There have been multiple early-phase clinical trials of various agents for the treatment of CRPC, and some are in phase III development. This review focuses on the key clinical trials of various treatment options of CRPC currently in use and under investigation.
Humans ; Imidazoles ; Immunotherapy ; Korea ; Male ; Mitoxantrone ; Molecular Targeted Therapy ; Nitro Compounds ; Palliative Care ; Prednisone ; Prostate ; Prostatic Neoplasms ; Taxoids ; Tissue Extracts ; United States ; United States Food and Drug Administration