Safety and efficacy of docetaxel,estramustine phosphate and hydrocortisone in hormone‐refractory prostate cancer patients

Objective: To assess the combination of docetaxel (DTX), estramustine phosphate (EMP) and hydrocortisone for patients with hormone‐refractory prostate cancer (HRPC). Methods: A total of 63 patients with HRPC were treated with a chemotherapeutic regimen including DTX, EMP, and hydrocortisone. Clinical and pathological features were correlated to serum prostate‐specific antigen (PSA) recurrence and survival rates. Incidence and degree of toxicities were also retrospectively reviewed. Results: A median of 11 courses of chemotherapy was administered per patient. PSA levels decreased by >50% in 32 (51%) patients and >90% in 18 (29%) patients. Median time to PSA progression was 6 months (range from 1 to 41 months) and median time of overall survival was 14 months (range from 1 to 56 months). In a univariate analysis to predict overall survival, PSA, hemoglobin, alkaliphosphatase, and performance status prior to the chemotherapy were significant factors. Despite grade 3–4 neutropenia in 87% of patients, grade 5 interstitial pneumonia in one patient and grade 4–5 myocardial infarction in two patients were recognized, the regimen seemed to be relatively safe. Conclusions: Combination chemotherapy with DTX, EMP and hydrocortisone provides survival benefits for patients with HRPC with an acceptable toxicity profile. We need to further evaluate who might benefit most from this regimen.     

Phase II trial of vinorelbine and estramustine in the treatment of metastatic hormone-resistant prostate cancer

The purpose of this study was to investigate the efficacy and safety of combination chemotherapy using estramustine and vinorelbine in chemotherapy-na?ve patients with hormone-resistant prostate cancer (HRPC). The patients (n = 54) received oral estramustine 840 mg/day on Days 1 to 14 and IV vinorelbine 25 mg/m(2) on Days 1 and 8 of every 3 wk cycle. The median number of cycles per patient was 9 (range, 1 to 27). Fifty-three patients were evaluable for toxicity and survival and 52 for prostate specific antigen (PSA) response. Median age was 68 (range, 46-80). PSA sustained decrease >50% was seen in 52% of patients (95% CI: 38-66%). A complete response was seen in 3 and a partial response in 12 of 25 patients with measurable disease, for an overall objective response of 60% (95% CI: 41-79%). Improvement in performance status was observed in 30 out of 43 evaluable for clinical benefit response. The median duration of response was 7 mo and median time to progression was 6 mo. The median survival time was 15 mo. The most common adverse event was mild gastrointestinal toxicity. In general, toxicity G3-4 was low: granulocytopenia Grade 3-4 (8%), thrombocytopenia Grade 3 (6%), and anemia Grade 3 (13%). Other Grade 3 toxicities included deep vein thrombosis (4%), hepatic (2%), cardiac ischemia (2%), fatigue (6%), and sensory neuropathy (2%). There were 2 treatment-related deaths (4%). We conclude that vinorelbine and estramustine as used in this trial is an efficacious and well-tolerated therapeutic regimen in the management of HRPC.     

Prospective study of estramustine phosphate for hormone refractory prostate cancer patients following androgen deprivation therapy

INTRODUCTION: Estramustine phosphate (EMP) in combination with other cytotoxic agents has been widely used in clinical trials as an anti-tumor agent for the treatment of hormone-refractory prostate cancer (HRPC). However, few prospective studies have considered the efficacy of EMP monotherapy for HRPC patients following androgen-deprivation therapy (ADT), given the availability of methods to measure prostate-specific antigen (PSA) levels in the serum. We therefore initiated a prospective study to determine whether EMP is efficient for HRPC following ADT using changes in PSA levels as the major endpoint. METHODS: After a diagnosis of anti-androgen withdrawal syndrome had been excluded, 34 patients with HRPC who showed an elevated serum PSA level in 3 or more sequential tests following ADT were treated orally with 560 mg/day of EMP. The clinical stage and the median PSA value for inclusion in the study were D2 and 25.9 (range 6.5-540.8) ng/ml, respectively. Treatment was continued until evidence of disease progression reappeared or until severe adverse effects appeared. RESULTS: Of the 34 patients enrolled, 29 were evaluated, while the other 5 (15%) patients were discontinued due to severe gastrointestinal side effects. Seven of the 29 patients (24%) showed a decrease of 50% or greater in serum PSA levels from the initially elevated values, with the median duration of PSA response being 8.0 (range 2.2-18.8) months. Baseline PSA, hemoglobin, alkaline phosphatase, lactate dehydrogenase, performance status, and length of time of initial hormonal treatment did not correlate with the PSA response. With a median follow-up time of 20.0 (range 3.2-45.6) months, the cancer-specific survival rate at 2 years was 83% in the PSA responders and 44% in the non-responders. The PSA response was correlated with cancer-specific survival (p = 0.029). CONCLUSIONS: Following ADT one quarter of HRPC patients responded to EMP, with more than 50% of patients showing a decrease in PSA levels and an enhanced survival rate.     

Docetaxel, vinorelbine, and zoledronic acid as first-line treatment in patients with hormone refractory prostate cancer: a phase II study

ObjectivesCombining antineoplastic agents is the key to improving the treatment options for men with hormone refractory prostate cancer (HRPC). The current study investigated the combination of docetaxel, vinorelbine, and zoledronic acid as a first-line treatment for HRPC.MethodsPatients were treated repeatedly with docetaxel (25 mg/mq) and vinorelbine (10 mg/mq) intravenously for three consecutive weeks followed by a 1-wk rest until disease progression or side effects. Zoledronic acid was administered every 4 wk. Changes in prostate-specific antigen (PSA) levels and objective responses were evaluated after two and three cycles, respectively. Toxicity and pain evaluation, based on pain intensity reduction and analgesic drug reduction, were assessed every cycle.ResultsForty men with HRPC (median age: 65 yr) were treated. Among 38 evaluable patients, complete and major PSA responses were observed in seven (18%) and 12 (32%), respectively; a partial objective response was observed in six of 15 (40%) patients with measurable disease. Neutropenia (25%) was the most important grade 3 haematologic toxicity observed. Only three patients (7.5%) reported grade 4 neutropenia. Nineteen patients (47.5%) achieved a reduction of pain intensity and analgesic drug use after two cycles. Median progression-free survival was 7 mo (95% CI: 2–10 mo), with a median overall survival of 17 mo (95% CI: 6–22 mo).ConclusionsThe combination of docetaxel, vinorelbine, and zoledronic acid is associated with improvement in biochemical, objective, and pain responses and is well tolerated as a first-line treatment for HRPC.     

Bi-weekly epirubicin, etoposide and low-dose dexamethasone for hormone-refractory prostate cancer

BACKGROUND: Recent studies have demonstrated the efficacy and favorable toxicity profile of chemotherapy regimens given at lower doses and frequent intervals. The aim of our study was to evaluate the efficacy and toxicity of a bi-weekly chemohormonal regimen consisting of epirubicin, etoposide, and low-dose dexamethasone (EED) in patients with hormone-refractory prostate cancer (HRPC). METHODS: We treated a total of 32 patients who had failed hormonal therapy and antiandrogen withdrawal. Chemotherapy was given every 2 weeks and consisted of epirubicin (30 mg/m2 intravenously, day 1) and etoposide (50 mg/m2 orally, days 1-7). Dexamethasone (1.5 mg orally, every other day) was given continuously until disease progression. Twenty patients (63%) had received prior treatment with estramustine phosphate. Each patient's pain response was evaluated according to analgesic use. Toxicity was graded using the Common Toxicity Criteria (version 2.0). RESULTS: Prostate-specific antigen (PSA) levels showed a decline of 50% or greater in 16 of 32 patients (50%, 95% confidence interval [CI], 32-68%) with a median time to biochemical progression of 5 months (range, 4-9 months). The median survival for all patients was 10.5 months (range, 3-35 months). Four of 10 patients (40%) with measurable soft tissue lesions achieved partial response according to standard criteria. Eleven of 23 symptomatic patients (48%, 95% CI, 27-69%) experienced an improvement in pain with a median duration of 6 months. The regimen was tolerated well by the patients, with only four patients (12%) having grade 3 leukopenia. CONCLUSION: Chemohormonal EED regimen proved to be active and well-tolerated in patients with HRPC.     

Combination chemotherapy with docetaxel, estramustine and suramin for hormone refractory prostate cancer

PURPOSE: To investigate more effective chemotherapy against hormone refractory prostate cancer (HRPC) with the combination of estramustine (EM), docetaxel, and suramin. PATIENTS AND METHODS: A total of 42 patients with symptomatic, progressive HRPC were included in this study. We evaluated the activity of the following schedule: EM 10 mg/kg orally daily on Days 1 to 21 every 28 days, docetaxel 70 mg/m(2) IV on Day 2 every 28 days and a total doses of 2150 mg of suramin in every cycle. Treatment was continued until disease progression or excessive toxicity. RESULTS: Median follow-up was 23.4 months. A median of 8.8 consecutive cycles was administered per patient. In the 25 patients with lymphadenopathy, there were three (12%) complete and 18 (72%) partial responses for a measurable disease response rate of 84%. Levels of prostatic specific antigen (PSA) decreased by greater than 50% in 100% of patients and by greater than 90% in 76.2%. The median time to progression was 57 weeks and median overall survival was 132 weeks. A decline in PSA of > or =50% lasting > or =30 days was significantly associated with a prolonged median time to progression and median overall survival. Tumor volume reduction and/or antitumor treatment effects were observed in 88% of patients. A significant decrease in mean pain score from 7.8 (range, 6-10) to 2.2 (range, 0-4) (P < 0.001) was achieved in 78%. Of patients with bone metastasis, 30.5% demonstrated a partial response. The mean Eastern Cooperative Oncology Group (ECOG) performance score improved from 2.8 to 1.5 at the end of treatment period. There was no therapy-related death. The predominant toxicities were Grade 3 or 4 leukopenia in 33.3%, anemia in 21%, thrombocytopenia in 21.4%, cardiac ischemia in 4.7%, and rash in 4.7%. CONCLUSION: The combination of docetaxel, EM, and suramin is a highly effective regimen for HRPC. Although hematologic and gastrointestinal toxicities were modest, these were easily managed medically.     

9-Nitrocamptothecin as second line chemotherapy for men with progressive, metastatic, hormone refractory prostate cancer: Results of the CALGB 99901

BACKGROUND: Institution of early hormone therapy in the PSA era coupled with demonstration of clinical benefit with chemotherapy in hormone refractory prostate cancer (HRPC) and acceptance of PSA decline as a surrogate for response has resulted in introduction of chemotherapy earlier in the natural history of disease. There now exists a need to identify, effective agents for second line chemotherapy. 9-nitrocamptothecin (9-NC) a novel, oral camptothecin analogue was tested as second line chemotherapy for patients with progressive hormone refractory prostate cancer. PATIENTS AND METHODS: Eligible patients had metastatic hormone refractory prostate cancer with performance status (0-1) following progression on at least 1 prior cytotoxic chemotherapy. 9-NC was administered orally at the dose of 1.5 mg/m2/d for 5 days each week for 3 weeks, followed by rest for 1 week. Response was evaluated after 2 cycles according to the guidelines set forth for Phase II trials in HRPC by the PSA working group. RESULTS: Thirty-five patients were recruited to the study within a period of 6 months; 33 were evaluable for analysis. No patients had a >50% decline in PSA levels. Two out of 8 (25%) patients with measurable disease and 5/25 (20%) patients with nonmeasurable disease showed stable disease. The median time to disease and PSA progression was 2 months [95% confidence interval (CI), 0.9-2.8]. The median overall survival was 10 months (95% CI = 5-12). Seven patients are alive after a median follow-up of 23 months. CONCLUSIONS: 9-nitrocamptothecin failed to elicit clinical or PSA responses. Further study in pretreated HRPC patients is not warranted.     

Hormonal chemotherapy for hormone-refractory prostate cancer

To our knowledge, no standard chemotherapy for patients with hormone-refractory prostate cancer (HRPC) has been established. Since most patients with HRPC are elderly and have bone metastasis, cytotoxic chemotherapy causes them to be at high risk for myelosuppression. Therefore, chemotherapeutic agents with low toxicity and good compliance should be elected. We conducted three regimens for HRPC on an outpatient basis. Eligibility criteria were defined as serial rising PSA values on 3 or more occasions at least 2 weeks apart or radiological new or extensive lesions under hormonal therapy. The first regimen is comprised of cyclophosphamide (CPM), 100 mg/day, UFT, 400 mg/day, and estramustine phosphate (EMP), 560 mg/day in two daily fractions. The second regimen is comprised of an oral administration of dexamethasone (DEX) (0.5-2 mg/day). The third regimen is comprised of DEX, 1 mg/day, cyclophosphamide, 100 mg/day and UFT, 400 mg/day in two daily fractions. Post-therapy prostate-specific antigen (PSA) level in serum, objective response on bone scan or measurable disease, and symptomatic response on bone pain were assessed. All regimens showed clinical efficacy with mild toxicity. Indications and limitations of these regimens are discussed. Further, the combination trials of taxane and EMP in patients with HRPC are reviewed.     

Combination chemotherapy with paclitaxel,estramustine and carboplatin for hormone refractory prostate cancer

PURPOSE: The activity of estramustine phosphate is synergistic with paclitaxel against hormone refractory prostate cancer. Moreover, the single agent activity of carboplatin has demonstrated a 17% response rate in measurable disease. Therefore, we conducted a prospective trial to establish more effective chemotherapy consisting of paclitaxel, estramustine phosphate and carboplatin for hormone refractory prostate cancer. MATERIALS AND METHODS: The study included 32 patients with hormone refractory prostate cancer. Prior chemotherapy was accepted. Patients were treated with 100 mg./m.2 paclitaxel intravenously weekly, 10 mg./kg. estramustine phosphate orally daily and carboplatin intravenously to an area under the curve of 6 on day 1 of every 4-week cycle. Treatment was continued until disease progression or excessive toxicity. RESULTS: Of the 32 patients 30 were assessable for response. A median of 7 consecutive cycles was administered per patient. Ten patients had received prior cytotoxic chemotherapy. Levels of prostate specific antigen decreased by greater than 50% in 100% of patients and by greater than 90% in 56.7%. Partial response was obtained in 61.1% of measurable lesions. Consumption of medication for cancer induced pain was reduced in 89.5% of patients. Tumor volume reduction and/or antitumor therapeutic effects were exhibited in 81.0% of patients with positive biopsy. At a median followup of 48 weeks median time to progression was 48 weeks and median overall survival was 95 weeks. Two patients suffered myocardial infarction and hepatic insufficiency, respectively, and discontinued treatment during the first cycle. Major toxicities were grade 3 or 4 anemia in 59.4% of patients, leukopenia in 37.5%, thrombocytopenia in 28.1% and neuropathy in 12.5%. However, all toxicity was temporary and reversible with dose reduction or temporary cessation of chemotherapeutic agents. CONCLUSIONS: Paclitaxel, estramustine phosphate and carboplatin chemotherapy was extremely effective for hormone refractory prostate cancer. Although hematological and neurotoxicity were modest, this therapy may be more manageable with lower doses.     

Phase II study of weekly paclitaxel for docetaxel-resistant metastatic breast cancer in Japan

The purpose of the study was to evaluate the efficacy of weekly paclitaxel (PTX) against metastatic breast cancer (MBC) that was resistant to docetaxel (DTX) given every 3 weeks. A multicenter phase II study was performed. Women with MBC resistant to DTX were eligible for enrollment. DTX resistance was defined as no tumor response to DTX and stable disease, partial response, or complete response to DTX preceding disease progression. PTX 80 mg/m(2) was administered over 1 hour once a week for 3 weeks per 4-week cycle. Among 47 enrolled patients, 46 patients were assessable for response and toxicity. The overall objective response rate (complete responses [CRs] and partial responses [PRs]) was 17.4% and overall clinical benefit rate (CRs, PRs, and stable disease >or=24 weeks) was 26.1%. The median time to progression was 11 weeks. There were a few severe hematologic toxicities related to the therapy, with grade 4 neutropenia (4.3%) and thrombocytopenia (2.2%). Grade 3 anaphylaxis and grade 3 neuropathy were observed in one patient (2.2%) each. The median delivered dose intensity was 77.6 mg/m(2)/week, 97.1% of the planned dose intensity. Weekly PTX has activity in patients with MBC resistant to DTX every 3 weeks.     

Combination chemotherapy with docetaxel and cisplatin in patients with hormone-refractory prostate cancer

We investigated the efficacy of docetaxel and cisplatin for hormone-refractory prostate cancer (HRPC). Thirteen patients with HRPC were treated with 30 mg/m2 docetaxel weekly for 3 weeks and 70 mg/m2 cisplatin on day 1. Treatment was repeated every 21 days. They received 2 cycles and were evaluated for the responses to serum prostate-specific antigen (PSA) and tumor size. Ten (77%) of the 13 patients showed a 50% or greater decrease in PSA with a median time to progression of 3 months. One of the 2 patients with measurable soft tissue disease showed a reduction in disease. No severe toxicity of this regimen was observed. Combination chemotherapy with docetaxel and cisplatin in patients with HRPC was well tolerated and efficatious with a significant decrease in serum PSA and measurable disease.     

Long-term disease stabilization by docetaxel plus estramustine for castration-resistant prostate cancer : report of a case

Chemotherapy with docetaxcel (DTX) plus estramustine (EMP) for castration-resistant prostate cancer (CRPC) was started 30 months after the patient, a 65-year-old man, was diagnosed as having advanced prostate cancer cT3aN1M1 (OSS) with an initial PSA of 490 ng/ml. Prostate biopsy specimens revealed moderately differentiated adenocarcinoma, Gleason's sum 4＋5. He was treated with DTX 30 mg/m2 on day 2 and oral EMP 560 mg/day days 1-3 weekly for 3 out of 4 weeks. PSA at start of DTX plus EMP was 81.7 ng/ml, and that after 59 months was 66.6 ng/ml. No objective change in computed tomography and bone scan were observed. He also had no cancer-related symptoms and activity of daily life was good. Chemotherapy was interrupted twice because of pleural effusion and dyspnea by DTX, at 3 and 4 months, respectively, long-term disease stabilization was obtained by this treatment. Other adverse events including interstitial pneumonia, cardiovascular disorders and myelosuppression were not observed. He was maintained on the same chemotherapy. DTX plus EMP chemotherapy is an effective treatment for CRPC patients. Continuing this therapy it is important to survey and control adverse events caused by DTX and EMP carefully.     

Evaluation of docetaxel plus estramustine in the treatment of patients with hormone-refractory prostate cancer

Objectives:   To investigate the feasibility and efficacy of docetaxel-based chemotherapy in patients with hormone-refractory prostate cancer (HRPC).
Methods:   Forty-six consecutive HRPC patients treated between January 2003 and March 2008 were included in this analysis. Docetaxel was given at a dose of 35 mg/m² twice every 3 weeks and oral estramustine concurrently for three consecutive days during weeks 1 and 2 of each cycle. During each treatment week, the dose of estramustine was 1260 mg on the first day, 980 mg on the second day and 840 mg on the third day. Patients were premedicated with 4 mg twice a day of oral dexamethasone for three consecutive days. Treatment was continued until evidence of disease progression or unacceptable toxicity. Prostate-specific antigen (PSA) levels were evaluated at least once every 4 weeks.
Results:   Patients received a median of three cycles of chemotherapy. Of the evaluable 46 patients, 25 (54%) had a ≥50% PSA decline and 12 (26%) had a ≥75% PSA decline. Median time to PSA progression and overall survival time were 10.1 and 27.0 months, respectively. Median follow-up was 15.0 months. Major severe toxicities were grade 3 or 4 leukopenia in five (11%) patients. Mild toxicities included grade 1 or 2 nausea in eight (17%) patients. Two patients could not continue the treatment because of interstitial pneumonitis and a gastric hemorrhage, respectively.
Conclusions:   Docetaxel plus estramustine chemotherapy represents an active and well tolerated treatment for Japanese HRPC patients.     

Weekly docetaxel and vinorelbine (VIN-DOX) as first line treatment in patients with hormone refractory prostate cancer

BACKGROUND: The current study investigated the clinical benefit, the impact on biochemical and objective response and tolerability of weekly docetaxel with vinorelbine (VIN-DOX) in symptomatic patients with hormone refractory prostate cancer (HRPC). METHODS: Patients were treated with docetaxel 25 mg/m2 and vinorelbine 20 mg/m2, intravenously for 6 consecutive weeks followed by a 2 week rest repeatedly until disease progression. Clinical benefit evaluations, based on Karnofsky performance status (KPS) and pain measure, were assessed weekly during therapy. A clinical benefit response was defined as a sustained (> or =4 weeks) improvements in one of these parameters. Changes in prostate-specific antigen (PSA) levels, tumoral response and toxicity also were evaluated. RESULTS: 19 men (median age 68 years), were treated. Overall, 42% of patients achieved a KPS significant change and positive pain response; 47% achieved a 50% or greater reduction in PSA. The objective response rate was observed in 2 of 9 patients with measurable disease (22%). The most important toxicity was neutropenia (Grade 3 = 32%). CONCLUSIONS: The combination of weekly VIN-DOX appears to be feasible. VIN-DOX was found to be associated with improvement in clinical benefit response and biochemical response and well tolerated as first line treatment in HRPC.     

A randomized study of docetaxel and dexamethasone with low- or high-dose estramustine for patients with advanced hormone-refractory prostate cancer

OBJECTIVE: To test the combination of docetaxel with two different doses of estramustine in patients with hormone-refractory prostate cancer (HRPC), to improve response rates and to lower side-effects, as docetaxel-based chemotherapy is an increasing option for men with advanced HRPC, and alone or combined with estramustine, docetaxel improves median survival. PATIENTS AND METHODS: In all, 72 patients with metastatic HRPC were randomly assigned to receive docetaxel (70 mg/m(2) intravenously, on day 2 every 21 days) and estramustine (3 x 280 mg/day oral starting 1 day before docetaxel, for 5 consecutive days) for arm A, or estramustine (3 x 140 mg/day oral starting 1 day before docetaxel, for 3 consecutive days) for arm B. Premedication with oral dexamethasone at a total daily dose of 16 mg, in divided doses twice a day was administered in arm A on day 1-5 and in arm B on day 1-3. Initially, six cycles were administered. Chemotherapy was restarted after a significant increase in prostate-specific antigen (PSA) level. Patients were monitored for any measurable PSA response and toxicity. RESULTS: Between the arms there was no statistically significant difference in time to progression and overall survival. However, treatment B had less treatment-related toxicity than A. Independent prognostic variables were baseline factors like PSA level, haemoglobin level, Eastern Cooperative Oncology Group performance status, and bone pain at presentation. CONCLUSIONS: In this randomized phase II study the combination of docetaxel and estramustine had substantial activity in HRPC, with a significant incidence of severe toxicity, both haematological and not. Nevertheless, treatment-related toxicity was predictable and manageable. There was no better effect with a higher dose of estramustine with docetaxel than for a lower dose. There was a slight tendency to higher toxicity for high-dose estramustine but this was not statistically significant. The present results support the assertion that estramustine is not necessary in docetaxel-based treatment regimens.     

Combination chemotherapy of docetaxel and UFT against hormone refractory prostate cancer

Docetaxel-based chemotherapy has been shown to be effective and well tolerated by Japanese patients with metastatic hormone-refractory prostate cancer (HRPC). This study was undertaken to assess the feasibility of docetaxel in combination with UFT (a combination of tegafur and uracil) in Japanese patients with HRPC. Ten patients aged 60-86 years with HRPC, who were pre-treated with hormonal therapy and expected to have more than 3 month survival and without major organ dysfunction, were included in this study. Treatment consisted of docetaxel 70 mg/m2 every 3 weeks plus UFT 260 mg/m2 /day. The primary end point was prostate-specific antigen (PSA) response, and the secondary end points included progression-free survival and toxicity. Nine patients were evaluable for efficacy and toxicity. The PSA response rate was 50% (1 CR and 4 PR). The most common non-hematological adverse events (of any grade) possibly related to treatment were neutropenia and anorexia. Grade 3/4 neutropenia and anorexia occurred in 50 and 20% of patients, respectively. The combination of docetaxel and UFT was feasible and active in Japanese patients with HRPC, with a manageable adverse-event profile similar to that observed in lung cancer chemotherapy.     

Serum PSA half-life as a predictor of survival for hormone-refractory prostate cancer patients: modelization using a standardized set of response criteria

OBJECTIVE: Changes of serum prostate-specific antigen (PSA) during chemotherapy have been validated as a marker of response for hormone-refractory prostate cancer (HRPC) patients. We retrospectively established new response criteria to assess the risk of death. METHODS: Two hundred fifty-six chemonaive HRPC patients treated with chemotherapy were included in the analysis. According to PSA half-life (HL) dynamics, three response categories were defined: responders (R), late-progressors (LP) and initial-progressors (IP), that were compared with Working Group (WG) criteria. PSA HL time to failure (TTF) and overall survival (OS) were estimated and compared between HT categories. Multivariate regression analysis was performed to isolate the impact on OS of these response categories. A new predictor of survival, delta-time PSA interval (DeltaT) was described. RESULTS: PSA HL categories were strongly related with WG criteria (P = 0.0001). PSA HL TTF differed among PSA HL categories: 4.2, 2.3, and 0.9 months for R, LP, and IP patients, respectively, and their respective median OS were 27, 19.7, and 12.3 months (P = 0.0001). For DeltaT > or = 3 versus <3 months, median OS significantly differed: 24.9 months versus 13.2 months (P = 0.0001). CONCLUSIONS: PSA HL dynamics during chemotherapy were able to accurately predict survival, earlier than WG-defined progression criteria. This criterion should be prospectively evaluated in randomized trials for HRPC patients in order to better estimate the risk of death.     

The Canadian Uro-Oncology Group multicentre phase II study of docetaxel administered every 3 weeks with prednisone in men with metastatic hormone-refractory prostate cancer progressing after mitoxantrone/prednisone

OBJECTIVE

To investigate the use of docetaxel 75 mg/m² intravenously every 3 weeks plus prednisone 5 mg orally twice daily in men with metastatic hormone‐refractory prostate cancer (HRPC) progressing after first‐line mitoxantrone/prednisone (MP), the primary outcome being progression‐free survival with prostatic‐specific antigen (PSA) and pain response, toxicity and quality of life (QoL) also assessed.

PATIENTS AND METHODS

Thirty patients from four centres were enrolled in the study; all had had previous MP for symptomatic, metastatic HRPC and all had castrate levels of testosterone maintained during therapy.

RESULTS

At enrolment, the median age was 69 years, the mean PSA level was 324 ng/dL, and 86% of patients reported pain. There was a PSA response in 57% of the men and a reduction in pain in >60%; the overall QoL was maintained. There were four cases of febrile neutropenia and two treatment‐related deaths. The median progression‐free and overall survival were 5 and 15 months, respectively.

CONCLUSION

Docetaxel was associated with high rates of PSA and pain response in this study. Non‐haematological toxicity was similar to that during first‐line treatment, but rates of febrile neutropenia and toxic death appeared to be slightly higher. In selected patients with progressive metastatic HRPC previously treated with mitoxantrone, docetaxel appears to be a beneficial therapeutic option.     

多西紫杉醇治疗激素难治性前列腺癌的研究

目的研究多西紫杉醇3周方案治疗激素难治性前列腺癌的疗效、毒副反应。方法对HRPC患者进行3周方案化疗：多西紫杉醇75mg／m2（第一天）,泼尼松5mg,口服hid,21d为一周期。反应严重的患者之后的给药剂量改为70mg／m2。观察患者的前列腺特异性抗原水平、病灶的变化、毒副反应。结果12例患者经治疗后PSA均有下降,5例PSA下降〉50％。治疗前后PSA中位数分别为28和18,两者比较有统计学差异。复查MRI中2例出现病灶减小。所有患者骨扫描未见新发灶,骨痛的患者中50％有不同程度缓解。主要的副反应为骨髓抑制。结论多西紫杉醇3周方案对于我国HRPC患者的疗效是肯定的,但毒副反应对化疗进程影响很大,本研究建议将不能耐受的患者药物剂量降为70mg／m2。     

3H-胸苷酸掺入法对选择前列腺癌化疗方案的价值

目的为临床选择激素难治性前列腺癌(HRPC)的化疗方案提供参考.方法采用3H-胸苷酸(3H-TdR)掺入法检测了20例HRPC细胞对常用化疗药物的敏感性.结果HRPC对单药的体外敏感性依次为足叶乙苷(VP16)＞阿霉素(ADM)、5-氟尿嘧啶(5-FU)、雌二醇氮芥(EMP)＞长春花碱(VLB)＞顺铂(DDP);二药联合可使敏感性进一步提高,依次为EMP加VP1 6、5-FU加ADM＞EMP加VLB＞5-FU加DDP三药联用抑瘤作用更强,EMP加VLB加APM、5 FU加ADM加DDP＞EMP加VLB加DDP.结论3H-TdR掺入法有助于化疗方案的选择,对HRPC以联合化疗效果较好.