The development and progression of metastatic castration-resistant prostate cancer is the major challenge in the treatment of advanced prostate cancer. The androgen receptor signaling pathway remains active in metastatic castration-resistant prostate cancer. Docetaxel and cabazitaxel are the first- and second-line chemotherapy, respectively, for patients with metastatic castration-resistant prostate cancer. These two taxanes, in general, function by (i) inhibiting mitosis and inducing apoptosis and (ii) preventing microtubule-dependent cargo trafficking. In prostate cancer, taxanes have been reported to inhibit the nuclear translocation and activity of the androgen receptor. However, whether this is attainable or not clinically remains controversial. In this review, we will provide a comprehensive view of the effects of taxanes on androgen receptor signaling in prostate cancer.
Antineoplastic Agents, Phytogenic/therapeutic use* ; Humans ; Male ; Prostatic Neoplasms, Castration-Resistant/drug therapy* ; Receptors, Androgen/drug effects* ; Signal Transduction/drug effects* ; Taxoids/therapeutic use*

Chemotherapy in prostate cancer (PCa) has undergone dramatic landscape changes. While earlier studies utilized varying chemotherapy regimens which were found to be largely palliative in nature and hardly resulted in durable or meaningful responses, docetaxel resulted in the first chemotherapy agent that showed improvement in overall survival in metastatic castration-resistant prostate cancer (mCRPC). However, combination chemotherapy or any agents added to docetaxel have failed to yield incremental benefits. The improvement in overall survival as well as secondary endpoints of prostate-specific antigen (PSA) and time to recurrence when using docetaxel in the metastatic hormone-sensitive state has changed the standard of care for treatment of newly diagnosed de novo metastatic PCa. There are also promising results in locally advanced PCa and high-risk PCa in both the neoadjuvant and adjuvant settings. This review summarizes the historical as well as the more contemporary use of chemotherapeutic agents in PCa in varying states and phases of disease.
Antineoplastic Agents/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Chemotherapy, Adjuvant ; Docetaxel/therapeutic use* ; History, 20th Century ; History, 21st Century ; Humans ; Male ; Neoadjuvant Therapy ; Prostatic Neoplasms/surgery* ; Taxoids/therapeutic use*

Objective: To investigate the clinical effects of integrated traditional Chinese and Western medicine in the treatment of castration-resistant prostate cancer (CRPC). METHODS: A total of 54 CRPC patients were randomly divided into a control and a trial group, all treated by endocrine therapy (oral Bicalutamide at 50 mg per d plus subcutaneous injection of Goserelin at 3.6 mg once every 4 wk) and chemotherapy (intravenous injection of Docetaxel at 75 mg/m2 once every 3 wk plus oral Prednisone at 5 mg bid), while the latter group by Fuyang Huayu Prescription (a Traditional Chinese Medicine ［TCM］ prescription for tonifying yang and dispersing blood stasis) in addition, for a course of 24 weeks. Comparisons were made between the two groups of patients in the level of serum prostate-specific antigen (PSA), Karnofsky physical condition scores, function assessment of cancer therapy-prostate (FACT-P) scores, and TCM symptoms scores before and after 12 or 24 weeks of treatment. RESULTS: Compared with the baseline, the serum PSA level was significantly decreased after 12 weeks of treatment both in the control (［25.9 ± 39.3］ vs ［20.0 ± 21.1］ μg/L, P <0.05) and in the trial group (［22.1 ± 33.9］ vs ［17.9 ± 19.1］ μg/L, P <0.05), with no statistically significant differences between the two groups (P >0.05). At 24 weeks, however, the PSA levels in the control and trial groups were slightly increased to (23.1 ± 28.4) and (19.6 ± 23.5) μg/L, respectively, with no statistically significant differences in between (P >0.05). Karnofsky, FACT-P and TCM symptoms scores were all markedly improved in the trial group after 12 weeks of treatment (P <0.05) and remained stable at 24 weeks, but not in the control group either at 12 or at 24 weeks (P >0.05). CONCLUSIONS TCM Fuyang Huayu Prescription combined with endocrine therapy and chemotherapy is effective for CRPC.
Anilides ; administration & dosage ; Antineoplastic Agents, Hormonal ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Docetaxel ; Drug Administration Schedule ; Goserelin ; administration & dosage ; Humans ; Male ; Nitriles ; administration & dosage ; Prednisone ; administration & dosage ; Prostate-Specific Antigen ; blood ; Prostatic Neoplasms, Castration-Resistant ; blood ; drug therapy ; Taxoids ; administration & dosage ; Tosyl Compounds ; administration & dosage ; Treatment Outcome

PURPOSE: Docetaxel-based chemotherapy (DTX) improves overall survival (OS) of men with metastatic castration-resistant prostate cancer (mCRPC). Considering the potential existence of androgen receptors that remain active at this stage, we aimed to assess the impact of the combined use of androgen deprivation therapy (ADT) with DTX for mCRPC. MATERIALS AND METHODS: We performed a single-institutional retrospective analysis of patients with mCRPC who received either DTX alone (DTX group, n=21) or concurrent DTX and ADT (DTX+ADT group, n=26) between August 2006 and February 2014. All patients received DTX doses of 75 mg/m2 every three weeks for at least three cycles. In the DTX+ADT group, all patients used luteinizing hormone releasing hormone agonist continuously as a concurrent ADT. RESULTS: The median follow-up period was 24.0 months (interquartile range 12.0-37.0) for the entire cohort. The median radiographic progression-free survival (rPFS) was 9.0 months and 6.0 months in the DTX+ADT and DTX groups, respectively (log-rank p=0.036). On multivariable Cox regression analysis, concurrent administration of ADT was the only significant predictor of rPFS [hazard ratio (HR)=0.525, 95% confidence intervals (CI) 0.284-0.970, p=0.040]. The median OS was 42.0 and 38.0 months in the DTX+ADT and DTX groups, respectively (log-rank p=0.796). On multivariable analysis, hemoglobin level at the time of DTX initiation was associated with OS (HR=0.532, 95% CI 0.381-0.744, p<0.001). CONCLUSION: In chemotherapy-naive patients with mCRPC, the combined use of ADT with DTX improved rPFS. Our result suggests that the concurrent administration of ADT and DTX is superior to DTX alone.
Adenocarcinoma/blood/*drug therapy/secondary ; Aged ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Disease-Free Survival ; Gonadotropin-Releasing Hormone/administration & dosage/agonists ; Hemoglobins/metabolism ; Humans ; Male ; Middle Aged ; Prostatic Neoplasms, Castration-Resistant/blood/*drug therapy/pathology ; Retrospective Studies ; Survival Rate ; Taxoids/administration & dosage

OBJECTIVETo explore the safety and efficacy of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in preventing chemotherapy-induced neutropenia in patients with breast cancer and non-small cell lung cancer (NSCLC), and to provide the basis for clinical application.

METHODSAccording to the principle of open-label, randomized, parallel-group controlled clinical trial, all patients were randomized by 1∶1∶1 into three groups to receive PEG-rhG-CSF 100 μg/kg, PEG-rhG-CSF 6 mg, or rhG-CSF 5 μg/kg, respectively. The patients with breast cancer received two chemotherapy cycles, and the NSCLC patients received 1-2 cycles of chemotherapy according to their condition. All patients were treated with the combination chemotherapy of TAC (docetaxel+ epirubicin+ cyclophosphamide) or TA (docetaxel+ epirubicin), or the chemotherapy of docetaxel combined with carboplatin, with a 21 day cycle.

RESULTSThe duration of grade 3-4 neutropenia in the PEG-rhG-CSF 100 μg/kg and PEG-rhG-CSF 6 mg groups were similar with that in the rhG-CSF 5 μg/kg group (P>0.05 for all). The incidence rate of grade 3-4 neutropenia in the PEG-rhG-CSF 100 μg/kg group, PEG-rhG-CSF 6 mg group, and G-CSF 5 μg/kg group were 69.7%, 68.4%, and 69.5%, respectively, with a non-significant difference among the three groups (P=0.963). The incidence rate of febrile neutropenia in the PEG-rhG-CSF 100 μg/kg group, PEG-rhG-CSF 6 mg group and G-CSF 5 μg/kg group were 6.1%, 6.4%, and 5.5%, respectively, showing no significant difference among them (P=0.935). The incidence rate of adverse events in the PEG-rhG-CSF 100 μg/kg group, PEG-rhG-CSF 6 mg group and G-CSF 5 μg / kg group were 6.7%, 4.1%, and 5.5%, respectively, showing a non-significant difference among them (P=0.581).

CONCLUSIONSIn patients with breast cancer and non-small cell lung cancer (NSCLC) undergoing TAC/TA chemotherapy, a single 100 μg/kg injection or a single fixed 6 mg dose of PEG-rhG-CSF at 48 hours after chemotherapy show definite therapeutic effect with a low incidence of adverse events and mild adverse reactions. Compared with the continuous daily injection of rhG-CSF 5 μg/kg/d, a single 100 μg/kg injection or a single fixed 6 mg dose of PEG-rhG-CSF has similar effect and is more advantageous in preventing chemotherapy-induced neutropenia.

Antineoplastic Agents ; adverse effects ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; Breast Neoplasms ; drug therapy ; Carboplatin ; administration & dosage ; adverse effects ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; Cyclophosphamide ; administration & dosage ; adverse effects ; Epirubicin ; administration & dosage ; adverse effects ; Female ; Granulocyte Colony-Stimulating Factor ; therapeutic use ; Humans ; Incidence ; Induction Chemotherapy ; Lung Neoplasms ; drug therapy ; Neutropenia ; chemically induced ; epidemiology ; prevention & control ; Polyethylene Glycols ; Recombinant Proteins ; administration & dosage ; Taxoids ; administration & dosage ; adverse effects

OBJECTIVE: To systematically review the efficacy and safety of taxane, cisplatin, and fluorouracil (Tax-PF) as induction chemotherapy for advanced head and neck cancer. METHOD: Literature about the efficacy and safety of Taxane-cisplatin-fluorouracil as induction chemotherapy for advanced head and neck cancer was retrieved from digital databases of PubMed, Embase, SpringerLink, MEDLINE and the Cochrane Library before February 2015. Data extraction and quality assessment of included studies were conducted by two reviewers independently. Stata 13.0 was then used to perform Meta-analysis. RESULT: A total 7 randomized controlled trials involving 2,702 were included. The 3-year OS rate [HR = 1.14, 95% CI (1.03, 1.25), P < 0.01], 3-year PFS rate [HR = 1.24, 95% CI (1.08, 1.43), P < 0.01], 5-year OS rate [HR = 1.30, 95% CI (1.09, 1. 55), P < 0. 01], 5-year PFS rate [HR = 1.39, 95% CI (1.14, 1.70), P < 0.01] and ORR to chemotherapy [OR = 1.66, 95% CI (1.35, 2.05), P < 0.01] of the patients in the Tax-PF group were statistically superior to those in the PF group. In terms of toxicities, the incidence of febrile neutropenia [OR = 2.36, 95% CI (1.62, 3.46), P < 0.01], alopecia [OR = 8.22, 95% CI (3.99, 16.92), P < 0.01], diarrhea [OR = 1.57, 95% CI (1.05, 2.36), P< 0.05] and leucopenia [OR = 2.79, 95% CI (1.86, 4.21), P < 0.01] was higher in the Tax-PF group than that in the PF group. CONCLUSION The Tax-PF induction chemotherapy improved PFS and OS, and the ORR was better as compared to PF-based therapy regimens at the cost of a higher incidence of adverse events.
Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Bridged-Ring Compounds ; therapeutic use ; Cisplatin ; therapeutic use ; Fluorouracil ; therapeutic use ; Head and Neck Neoplasms ; drug therapy ; Humans ; Induction Chemotherapy ; Randomized Controlled Trials as Topic ; Taxoids ; therapeutic use

PURPOSE: Few data are available concerning the clinical outcome of abiraterone acetate treatment in patients with metastatic castration-resistant prostate cancer (mCRPC) in terms of the duration of androgen deprivation therapy (ADT) before diagnosis of CRPC. We investigated the clinical efficacy of abiraterone acetate according to the duration of ADT. MATERIALS AND METHODS: We reviewed the medical records of 20 patients with mCRPC who received abiraterone acetate after failure of docetaxel chemotherapy from May 2012 to March 2014 at Seoul National University Bundang Hospital. Clinical factors including prostate-specific antigen (PSA) nadir level, time to PSA nadir, PSA doubling time, PSA response, and modes of progression (PSA, radiologic, clinical) were analyzed. Disease progression was classified according to the Prostate Cancer Working Group 2 criteria. RESULTS: The mean age and PSA value of the entire cohort were 76.0+/-7.2 years and 158.8+/-237.9 ng/mL, respectively. The median follow-up duration was 13.4+/-6.7 months. There were no statistically significant differences in clinical characteristics between patients who received abiraterone acetate with ADT duration<35 months and those who received abiraterone acetate with ADT duration> or =35 months. There were also no significant differences in terms of PSA progression-free survival, radiologic progression-free survival, and clinical progression-free survival between patients with ADT duration<35 months and those with ADT duration > or =35 months. CONCLUSIONS: Although this was a retrospective study with a small sample size, we did not observe any statistically significant differences in the clinical response to abiraterone acetate between mCRPC patients with long ADT duration and those with short ADT duration in terms of disease progression-free survival.
Abiraterone Acetate/administration & dosage ; Aged ; Aged, 80 and over ; Androgen Receptor Antagonists/administration & dosage ; Antineoplastic Agents/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Disease Progression ; Drug Administration Schedule ; Humans ; Kallikreins/blood ; Male ; Neoplasm Metastasis ; Prostate-Specific Antigen/blood ; Prostatic Neoplasms, Castration-Resistant/*drug therapy ; Retrospective Studies ; Taxoids/administration & dosage ; Treatment Outcome

OBJECTIVEThe aim of this study was to analyze the efficacy and safety of paclitaxel liposomal and docetaxel for neoadjuvant chemotherapy of breast cancer.

METHODSWe retrospectively analyzed the clinical data of 188 operable patients with breast cancer who received neoadjuvant chemotherapy. According to the treatment regimens, they were divided into the group of paclitaxel liposome (86 patients) and group of docetaxel (102 patients) treatment. All the patients received a combination therapy with epirubicin and cyclophosphamide, i.e. neoadjuvant chemotherapy with three drugs, 21 days as a cycle, and a total of 6 cycles. Surgery was carried out three weeks after the end of chemotherapy, and the chemotherapy efficacy and adverse reaction of both groups were evaluated.

RESULTSPathological complete response (pCR) rate in the paclitaxel liposome group and docetaxel group was 10.5% and 9.8%, respectively, the objective response rate (ORR) was 80.2% and 79.4%, respectively, and the disease control rate (DCR) was 95.3% and 93.1%, respectively, showing a non-significant difference in therapy efficacy between the two groups (P > 0.05). Safety analysis indicated that all the occurrence rates of skin and nail toxic reaction, body fluid retention, oral mucositis, allergic reaction (such as facial blushing, chest distress, palpitation, dyspnea. etc.), and grade III-IV leukopenia and neutropenia in the paclitaxel liposome group were significantly lower than that of the docetaxel group (all P < 0.05).

CONCLUSIONSCompared with docetaxel, paclitaxel liposome has the same anti-tumor efficacy, but causes fewer and milder adverse reactions with a higher safety in the neoadjuvant chemotherapy for breast cancer.

Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Breast Neoplasms ; drug therapy ; Cyclophosphamide ; therapeutic use ; Epirubicin ; therapeutic use ; Female ; Humans ; Liposomes ; Neoadjuvant Therapy ; Neutropenia ; Paclitaxel ; therapeutic use ; Remission Induction ; Taxoids ; therapeutic use

PURPOSE: To investigate the relationship between rising patterns of prostate-specific antigen (PSA) before chemotherapy and PSA flare during the early phase of chemotherapy in patients with castration-resistant prostate cancer (CRPC). MATERIALS AND METHODS: This study included 55 patients with CRPC who received chemotherapy and in whom pre-treatment or post-treatment PSA levels could be serially obtained. The baseline parameters included age, performance, Gleason score, PSA level, and disease extent. PSA doubling time was calculated using the different intervals: the conventional interval from the second hormone manipulation following the nadir until anti-androgen withdrawal (PSADT1), the interval from the initial rise after anti-androgen withdrawal to the start of chemotherapy (PSADT2), and the interval from the nadir until the start of chemotherapy (PSADT3). The PSA growth patterns were analyzed using the ratio of PSADT2 to PSADT1. RESULTS: There were two growth patterns of PSA doubling time: 22 patients (40.0%) had a steady pattern with a more prolonged PSADT2 than PSADT1, while 33 (60.0%) had an accelerating pattern with a shorter PSADT2 than PSADT1. During three cycles of chemotherapy, PSA flare occurred in 11 patients (20.0%); of these patients, 3 were among 33 (9.1%) patients with an accelerating PSA growth pattern and 8 were among 22 patients (36.4%) with a steady PSA growth pattern (p=0.019). Multivariate analysis showed that only PSA growth pattern was an independent predictor of PSA flare (p=0.034). CONCLUSION: An exponential rise in PSA during anti-androgen withdrawal is a significant predictor for PSA flare during chemotherapy in CRPC patients.
Aged ; Aged, 80 and over ; Androgen Antagonists ; Antineoplastic Agents/*therapeutic use ; Follow-Up Studies ; Humans ; Karnofsky Performance Status ; Male ; Middle Aged ; Neoplasm Grading ; Predictive Value of Tests ; Prostate-Specific Antigen/*blood ; Prostatic Neoplasms, Castration-Resistant/*blood/*drug therapy/pathology ; Taxoids/*therapeutic use ; Tumor Markers, Biological/blood

OBJECTIVETo detect the expression of IGF1R and estrogen receptor, and to explore the relationship between their expression and the pathological complete response (pCR) rate of neoadjuvant chemotherapy (docetaxel plus epirubicin) in breast cancer patients.

METHODSWe selected 139 women with breast cancer who underwent neoadjuvant chemotherapy (docetaxel plus epirubicin), and detected the expression of IGF1R and estrogen receptor in the samples taken before chemotherapy by Immunohistochemistry. The association between their expression and pCR rate of neoadjuvant chemotherapy was analyzed.

RESULTSAmong the 139 cases, IGF1R was highly expressed in 45.3% (63/139) cases, and ER was positively expressed in 62.6% (87/139) cases. IGF1R was highly expressed in 54.0% (47/87) of the ER+ cases, significantly higher than that of ER- cases (30.8%, P<0.01). The overall pCR rate of all the 139 patients who received docetaxel plus epirubicin as neoadjuvant chemotherapy was 10.1% (14/139). The pCR rate was 19.2% (10/52) of the ER- patients and 4.6% (4/87) of the ER+ patients (P<0.05). The pCR rate was 10.5% (8/76) in the patients with low IGF1R expression and 9.5% (6/63) in the patients with high IGF1R expression (P>0.05). The patients with negative expression of ER and high expression of IGF1R showed the highest pCR rate (31.2%, P<0.01).

CONCLUSIONSBreast cancer patients with negative expression of ER and high expression of IGF1R are more sensitive to neoadjuvant chemotherapy of docetaxel plus epirubicin, and their pCR rate is significantly higher than that of other patients.

Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Biomarkers, Tumor ; Breast Neoplasms ; drug therapy ; metabolism ; Epirubicin ; administration & dosage ; Female ; Humans ; Immunohistochemistry ; Neoadjuvant Therapy ; Receptors, Estrogen ; metabolism ; Receptors, Somatomedin ; metabolism ; Taxoids ; administration & dosage