Androstadienes ; therapeutic use ; Antineoplastic Agents, Hormonal ; administration & dosage ; Aromatase Inhibitors ; administration & dosage ; Breast Neoplasms ; drug therapy ; Drug Administration Schedule ; Female ; Humans ; Nitriles ; administration & dosage ; Postmenopause ; Triazoles ; administration & dosage

OBJECTIVETo investigate the safety and medication cycles of intermittent androgen deprivation (IAD) in the treatment of aggressive prostate cancer.

METHODSBased on prostate cancer clinical staging, we divided 178 patients with aggressive prostate cancer into groups A (T3-4N0M0), B (TXN1M0) and C (TXNXM1) to receive maximum androgen blockage for at least 6 months till the PSA level remained at < or = 0.2 microg/L for 3 months, followed by an off-period (without medication). The on-period was initiated when the PSA level was > 4 microg/L, and then stopped again when it was < or = 0.2 microg/L. We recorded and compared the patients' age, baseline PSA levels, Gleason scores, duration of on- and off-period, and time to tumor progression.

RESULTSThe baseline PSA levels of the 3 groups were (27.5 +/- 14.6), (43.4 +/- 21.8) and (62.8 +/- 44.6) microg/L, P < 0.01; the follow-ups averaged (38.4 +/- 9.6), (33.1 +/-14.0) and (28.3 +/- 14.3) months; and the times from medication initiation to tumor progression were (37.4 +/- 6.6), (27.4 +/- 10.2) and (16.6 +/- 4.4) months, respectively. Group A showed a longer off-period and more medication cycles than B and C (P < 0.01). Nineteen patients completed 5 cycles and 2 died of cardiovascular events in group A. PSA elevation and cancer progression occurred after 3 cycles at most in group C. Six died in group B, 1 of metastatic prostate cancer, and 36 died in group C, 21 of metastasis.

CONCLUSIONFor local aggressive prostate cancer, IAD can effectively slow down tumor progression, reduce adverse events and improve patients' quality of life.

Aged ; Aged, 80 and over ; Androgen Antagonists ; administration & dosage ; therapeutic use ; Antineoplastic Agents, Hormonal ; administration & dosage ; therapeutic use ; Humans ; Male ; Middle Aged ; Prostatic Neoplasms ; drug therapy ; Treatment Outcome

BACKGROUNDAlthough previous clinical study revealed that bortezomib combined with dexamethasone had improved the outcomes of relapsed or refractory multiple myeloma (RRMM), the optimal dose combinations of bortezomib and dexamethasone remain unknown. This trial aimed to observe the efficacy and safety of different dose combinations of bortezomib and dexamethasone in the treatment of RRMM patients in China.

METHODSA total of 168 patients with relapsed multiple myeloma (MM) who were refractory to at lest two prior treatments were enrolled in this multicenter, open-label, non-randomized, prospective clinical trial. Twenty patients received 1.3 mg/m(2) of bortezomib twice weekly for 2 weeks of a 3-week cycle for up to 8 cycles and oral or intravenous dexamethasone 20 mg on the day of and after each bortezomib dose (group 1); 66 patients received less than 1.3 mg/m(2) (0.7 - 1.0 mg/m(2)) of bortezomib and dexamethasone 20 mg on the same schedule (group 2); 37 patients received 1.3 mg/m(2)2 of bortezomib and dexamethasone 40 mg (group 3) and 45 patients received less than 1.3 mg/m(2) (0.7 - 1.0 mg/m(2)) of bortezomib and dexamethasone 40 mg (group 4). The response was evaluated according to the criteria of the European Group for Blood and Marrow Transplantation and confirmed by an independent review committee. Adverse events were graded according to the National Cancer Institute Common Toxicity Criteria, version 3.0.

RESULTSThe median age of groups 1 to 4 was 61, 62, 56, and 60 years, respectively. Most patients were in stages II/III of MM and the most common subtype was IgG. The rate of overall response to bortezomib and dexamethasone of group 1 to 4 was 72.2% (13/18), 73.8% (48/65), 78.8% (26/33) and 78.0% (32/41) (P = 0.91), including a complete response rate of 22.2% (4/18), 20.0% (13/65), 33.3% (11/33) and 29.3% (12/41) (P = 0.67), respectively. There was no statistical significance in time to progression and overall survival among these 4 groups (P > 0.05). The most commonly adverse events of any grade in the entire 4 groups were fatigue, gastrointestinal effects, peripheral neuropathy and thrombocytopenia, and there was no significance in the number of adverse events among the 4 groups (P > 0.05) except that peripheral neuropathy was reported more frequently in group 3 (36.3%) than in group 2 (13.8%, P < 0.05) and group 4 (14.6%, P < 0.05).

CONCLUSIONSThe combination of bortezomib and dexamethasone was associated with high responses in Chinese RRMM patients. No significant differences of efficacy were detected in different dose combinations of bortezomib and dexamethasone. Moreover, low dose of bortezomib reduced the incidence of peripheral neuropathy without affecting outcome in the treatment of patients with RRMM in China.

Antineoplastic Agents ; administration & dosage ; Antineoplastic Agents, Hormonal ; administration & dosage ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Boronic Acids ; administration & dosage ; Bortezomib ; China ; Dexamethasone ; administration & dosage ; Drug Therapy, Combination ; Female ; Humans ; Male ; Middle Aged ; Multiple Myeloma ; drug therapy ; Neoplasm Recurrence, Local ; Prospective Studies ; Pyrazines ; administration & dosage

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

OBJECTIVETo evaluate the efficacy and safety of gonadotropin-releasing hormone analogue (GnRHa) triptorelin 11.25 mg 3-month sustained release formulations in the treatment of metastatic prostate cancer.

METHODSFrom January 2004 to March 2006, a randomized, parallel-controlled, multicenter clinical trial was conducted. One hundred and twenty-seven patients with documented metastatic prostate cancer were randomized to receive one injection of the 11.25 mg formulation triptorelin (n = 65) or three injections at 28-day intervals of the 3.75 mg formulation (n = 62). Changes from baseline of TPSA, prostate volume, testosterone, LH, FSH, PRL and estradiol were assessed over 3 months. Changes of the metastatic lesions were also observed and evaluated. The occurrences of adverse events were evaluated as well.

RESULTSAfter 3 months treatment, total PSA level decreased significantly from baseline both in 11.25 mg group and 3.75 mg group. At 30, 60 and 90 days, TPSA (median level) declined from 164.55 microg/L into 11.34, 4.12, 3.89 microg/L in 11.25 mg group, and from 101.38 microg/L into 6.88, 2.41, 2.57 microg/L in control group respectively. The patients ratio with over 90% decreasing from TPSA baseline were 78.6% and 75.5% respectively in two groups (P = 0.700). Prostate volume were also decreased significantly in both groups, median volume declined from 48.0 mm(3) into 21.5 mm(3) in 11.25 mg group and from 45.0 mm(3) into 21.0 mm(3) in 3.75 mg group. No significant differences were found between the two groups in changes of TPSA (P = 0.601) and prostate volume (P > 0.05). Both formulations were able to induce castration levels, 0.31 microg/L in 11.25 mg group and 0.26 microg/L in 3.75 mg group (P > 0.05). 13.8% and 17.7% of adverse events were recorded respectively in two groups, and no differences were found (P = 0.547).

CONCLUSIONAs a new long-acting sustained release formulation, triptorelin 11.25 mg is comparable to triptorelin 3.75 mg formulation in the aspect of efficacy and safety for the treatments of metastatic prostate cancer.

Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents, Hormonal ; administration & dosage ; therapeutic use ; Gonadotropin-Releasing Hormone ; analogs & derivatives ; therapeutic use ; Humans ; Male ; Middle Aged ; Prostatic Neoplasms ; drug therapy ; pathology ; Safety ; Treatment Outcome ; Triptorelin Pamoate ; administration & dosage ; therapeutic use

AIMTo investigate the mechanisms of action of transportation of liposomes and chitosan-coated liposomes containing leuprolide across rat intestine and Caco-2 cell.

METHODSEverted-gut technique and Caco-2 cell were used to study the transport properties of free leuprolide, liposomes and chitosan-coated liposomes containing leuprolide. Caco-2 cell was used to study the effect of chitosan concentration and the order of addition on the permeation of liposomes.

RESULTSThe transport of leuprolide was passive diffusion. Probably because the entrapment by liposomes prevents the transport of leuprolide across the rat intestine and Caco-2 cell, the permeation amount of leuprolide from liposomes was lower than that of the free drug. However, liposomes protected the leuprolide from degradation. Chitosan promoted the transport of leuprolide from liposomes and there was no obvious difference in enhancement effect from the concentration of 0.1% to 0.5%. On the other hand, the incubation of chitosan with liposomes may weak the enhancement effect of chitosan.

CONCLUSIONChitosan-coated liposomes showed both protection and enhancement effect, therefore, they may promote the oral absorption of leuprolide.

Animals ; Antineoplastic Agents, Hormonal ; administration & dosage ; pharmacokinetics ; Biological Transport ; drug effects ; Caco-2 Cells ; Chitosan ; chemistry ; pharmacology ; Drug Carriers ; Drug Delivery Systems ; Humans ; Jejunum ; metabolism ; Leuprolide ; administration & dosage ; pharmacokinetics ; Liposomes ; Particle Size ; Permeability ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo study the demethylation effect of arsenic trioxide (As2O3) on ERα-negative human breast cancer MDA-MB-435s cells and its possible mechanisms, and to observe its treatment efficacy in combination with tamoxifen (TAM) after ERα re-expression.

METHODSMTT assay was used to examine the inhibitory effect of As2O3 treatment alone or in combination with TAM on cell proliferation. A nude mouse xenograft model was used to further examine the treatment efficacy in vivo. MSP was used to detect the methylation status of ERα gene after treated with As2O3 in MDA-MB-435s cells and the transplanted tumor tissues. RT-PCR was used to detect the mRNA expression of DNMT1 and Erα. Western bolt was used to detect the DNMT1 and ERα protein expression. The diameter of xenograft tumors was measured weekly, and the tumor growth curve was drawn.

RESULTSThe level of proliferation of the MDA-MB-435s cells was significantly suppressed after treatment with different concentration of As2O3 alone or As2O3 combined with TAM, and the 4 µmol/L As2O3 + TAM treatment for 72 h showed the highest inhibition rate (62.6%). 1, 2, 4 µmol/L As2O3 had demethylation effect on MDA-MB-435s cells, and the DNMT1 mRNA and protein expression was inhibited and accompanied by ERα mRNA and protein re-expression. The unmethylation specific bands of ERα gene were enhanced after treated by As2O3 alone or As2O3 combined with TAM in the xenograft tumors. The expression of DNMT1 mRNA and protein was inhibited, and accompanied by ERα mRNA and protein re-expression. An significant decrease of volume and weight of the xenograft tumors in the As2O3 treated alone or combined with TAM groups was observed compared with those of the normal saline group or TAM alone group (P < 0.05), and the 4 mg/kg As2O3 + TAM group had the highest inhibition rate of tumor weight (79.5%) and volume (76.4%).

CONCLUSIONSERα can be re-expressed in ERα-negative breast cancer MDA-MB-435s cells after treated with As2O3 by inhibiting the DNMT1 activity. MDA-MB-435s cells are re-sensitized to endocrine therapy after ERα re-expression. As2O3 combined with TAM may provide a new therapeutic approach for patients with ERα-negative breast cancer in the clinic.

Animals ; Antineoplastic Agents ; administration & dosage ; pharmacology ; Antineoplastic Agents, Hormonal ; administration & dosage ; Antineoplastic Combined Chemotherapy Protocols ; pharmacology ; Arsenicals ; administration & dosage ; pharmacology ; Breast Neoplasms ; genetics ; metabolism ; pathology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; DNA (Cytosine-5-)-Methyltransferase 1 ; DNA (Cytosine-5-)-Methyltransferases ; DNA Methylation ; Dose-Response Relationship, Drug ; Estrogen Receptor alpha ; genetics ; metabolism ; Female ; Humans ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Oxides ; administration & dosage ; pharmacology ; RNA, Messenger ; metabolism ; Tamoxifen ; administration & dosage ; Tumor Burden ; drug effects ; Xenograft Model Antitumor Assays

OBJECTIVETo search for an effective hormonal therapy for delaying the progression of prostate cancer to androgen-independent prostate cancer (AIPC).

METHODSThis study included 93 cases of prostate cancer confirmed by transrectal ultrasound-guided biopsy, 22 treated by bilateral orchiectomy plus bicalutamide as a continuous androgen deprivation (CAD) therapy, and the other 71 by the intermittent androgen deprivation (IAD) therapy, the latter divided into a standard IAD group (n = 29) and a modified IAD group (n = 42) to be treated by maximum androgen blockage (MAB) until the serum PSA level decreased to less than 0.2 microg/L and the medication was maintained for 3 months. Entering the intermittent period, the patients of the standard IAD group discontinued medication, while those in the modified IAD group withdrew luteinizing hormone-releasing hormone analogue (LHRH-a) but continued the use of bicalutamide. MAB was resumed in these two groups when serum PSA manifested a continuous rise and went up to 4 microg/L until prostate cancer progressed to AIPC. Comparisons were made among the CAD, standard IAD and modified IAD groups in the follow-up time, time of progression to CRPC and treatment cycles.

RESULTSThe three groups of patients were well balanced in terms of demographics, baseline characteristics and follow-up time. The median times of progression to AIPC in the CAD, standard IAD and modified IAD groups were (26.50 +/- 4.15), (30.00 +/- 7.83) and (34.93 +/- 5.08) months, respectively, with statistically significant differences between the modified IAD group and the CAD (P = 0.001) and standard IAD (P = 0.032), but not between the latter two groups (P = 0.143). Kaplan-Meier survival curves showed a significantly longer median time of progression to AIPC in the modified than in the standard IAD group (P = 0.01). The mean cycle length was (16.13 +/- 3.33) months for the standard IAD group and (19.58 +/- 4.30) months for the modified IAD group, and the time off treatment of the first cycle was (9.6 +/- 3.2) months in the former and (14.2 +/- 3.7) months in the latter, with significant difference between the two groups (P = 0.001).

CONCLUSIONCompared with CAD and standard IAD, modified IAD therapy can significantly prolong the time of progression to AIPC in patients with prostate cancer.

Aged ; Aged, 80 and over ; Androgen Antagonists ; administration & dosage ; therapeutic use ; Anilides ; administration & dosage ; therapeutic use ; Antineoplastic Agents, Hormonal ; administration & dosage ; therapeutic use ; Disease Progression ; Humans ; Male ; Middle Aged ; Nitriles ; administration & dosage ; therapeutic use ; Prognosis ; Prostatic Neoplasms ; diagnosis ; drug therapy ; Tosyl Compounds ; administration & dosage ; therapeutic use ; Treatment Outcome

PURPOSE: Granulomas resulting from the administration of luteinizing hormone-releasing hormone analogues (LH-RH analogues) are thought to be very rare. We report on our clinical experience with injection-site granulomas that result from the administration of LH-RH analogues, and we evaluate the incidence rate of these granulomas. MATERIALS AND METHODS: We used the clinical records of 118 patients who were administered LH-RH analogues in 2005. We describe the clinical data of patients who experienced injection-site granulomas and evaluated the incidence rate. RESULTS: Five patients demonstrated injection-site granulomas due to LH-RH analogue administration. The incidence rate was 4.2% (5 of 118 patients). Most of the granulomas occurred after the first or second administration of 11.25mg of leuprorelin acetate. CONCLUSION: The occurrence of granulomas resulting from the administration of LH-RH analogues was thought to be very rare. Our study, however, revealed a higher incidence rate than expected, especially for leuprorelin acetate.
Aged ; Aged, 80 and over ; Antigens, CD/analysis ; Antigens, CD3/analysis ; Antigens, Differentiation, Myelomonocytic/analysis ; Antineoplastic Agents, Hormonal/administration & dosage/adverse effects ; Gonadotropin-Releasing Hormone/administration & dosage/*adverse effects/analogs & derivatives ; Goserelin/administration & dosage/adverse effects ; Granuloma/*etiology/metabolism/pathology ; Humans ; Injections, Subcutaneous/adverse effects ; Leuprolide/administration & dosage/adverse effects ; Male ; Prostatic Neoplasms/*drug therapy

OBJECTIVETo explore the action of pingxiao capsules (PXC) and its significance in the treatment of late stage mammary cancer (LSMC).

METHODSOne hundred and forty-two LSMC patients were randomized into four groups: the two single treated groups treated by endocrinotherapy (ET) alone (n = 27) and by chemotherapy alone (n=44) respectively, and the two PXC combined treated groups treated with PXC plus endocrinotherapy (n=27) or chemotherapy (n=44). The remission rate and progression time (TTP) of disease, the survival time and quality of life (QOL) of patients, and the adverse reaction were compared between the single treated groups and the combined treated groups.

RESULTSThe median progression time was obviously prolonged, and QOL improved in the combined treated groups than those in the single treated groups (P < 0.05), but no significant difference was found in the remission rate or adverse reaction between them.

CONCLUSIONPXC can improve QOL, prolong the progression time in patients of LSMC, and with less adverse reaction. It is worth spreading combination of PXC with chemo- or endocrino-therapy in clinical application for treatment of LSMC patients.

Adult ; Aged ; Antineoplastic Agents, Hormonal ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Breast Neoplasms ; drug therapy ; pathology ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Middle Aged ; Paclitaxel ; administration & dosage ; Phytotherapy ; Sepharose ; administration & dosage ; analogs & derivatives ; Tamoxifen ; therapeutic use