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Results for “PSA response”

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At least 55 records · Page 3Linked to original sources

PubMed1998

Prolonged prostate-specific antigen response in flutamide withdrawal syndrome despite disease progression.

Flutamide withdrawal syndrome is characterized by a decrease in prostate-specific antigen (PSA) after flutamide withdrawal in a subset of patients with progressing metastatic carcinoma of the prostate. It is generally hypothesized to be due to a point mutation in the androgen receptor that allows the antiandrogen to function as an agonist, leading to a dramatic and rapid PSA response. We describe a patient with androgen-independent prostate cancer in whom PSA continued to decrease for a period of 15 months after flutamide withdrawal. With continuing fall in PSA, the patient had unequivocal progression of disease seen on bone scan. This case illustrates the potential decoupling of PSA response from disease status in flutamide withdrawal. It also illustrates the need for continued clinical evaluation of patients with metastatic prostate cancer, even in the face of PSA response.

Aged↗

PubMed2003

Phase II study of abarelix depot for androgen independent prostate cancer progression during gonadotropin-releasing hormone agonist therapy.

PURPOSE: We determine the clinical efficacy of the gonadotropin-releasing hormone (Gn-RH) antagonist abarelix in patients with androgen independent prostate cancer, and measure its effect on serum follicle-stimulating hormone (FSH) and testosterone. MATERIALS AND METHODS: A total of 20 patients with prostate cancer progression during Gn-RH agonist therapy received 100 mg. abarelix depot by intramuscular injection on days 1, 15 and 29, and then every 28 days for up to 24 weeks. Gn-RH agonist therapy was not continued. Patients who met criteria for prostate specific antigen (PSA) response after 24 weeks of therapy could receive treatment for up to 52 weeks. PSA response was the primary end point and was defined as a 50% decrease confirmed 4 weeks later. Secondary end points of this study were the effect of therapy on serum FSH and testosterone. RESULTS: No patient met the criteria for PSA response. At the end of the 6 cycles of therapy 2 patients remained stable without PSA progression or other signs of disease progression. Median time to progression was 8 weeks (95% CI 5.7-10.3). Mean serum FSH decreased by more than 50% from a baseline of 5.7 IU/l. (95% CI 4.2-7.1) and remained suppressed throughout the observation period. Mean serum testosterone did not change after 4 and 8 weeks of therapy and remained in the anorchid range. Treatment was well tolerated with no grade 3 or higher toxicity. CONCLUSIONS: Treatment of androgen independent prostate cancer with abarelix decreases circulating FSH and maintains anorchid testosterone but does not result in clinical responses.

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PubMed2006

Phase I-II prospective dose-escalating trial of lycopene in patients with biochemical relapse of prostate cancer after definitive local therapy.

OBJECTIVES: To report a prospective trial of lycopene supplementation in biochemically relapsed prostate cancer. METHODS: A total of 36 men with biochemically relapsed prostate cancer were enrolled in a dose-escalating, Phase I-II trial of lycopene supplementation. Six consecutive cohorts of 6 patients each received daily supplementation with 15, 30, 45, 60, 90, and 120 mg/day for 1 year. The serum levels of prostate-specific antigen (PSA) and plasma levels of lycopene were measured at baseline and every 3 months. The primary endpoints were PSA response (defined as a 50% decrease in serum PSA from baseline), pharmacokinetics, and the toxicity/tolerability of this regimen. RESULTS: A total of 36 patients were enrolled. The median age was 74 years (range 56 to 83), with a median serum PSA at entry of 4.4 ng/mL (range 0.8 to 24.9). No serum PSA responses were observed, and 37% of patients had PSA progression. The median time to progression was not reached. Toxicity was mild, with 1 patient discontinuing therapy because of diarrhea. Significant elevations of plasma lycopene were noted at 3 months and then appeared to plateau for all six dose levels. The plasma levels for doses between 15 and 90 mg/day were similar, with additional elevation only at 120 mg/day. CONCLUSIONS: Lycopene supplementation in men with biochemically relapsed prostate cancer is safe and well tolerated. The plasma levels of lycopene were similar for a wide dose range (15 to 90 mg/day) and plateaued by 3 months. Lycopene supplementation at the doses used in this study did not result in any discernible response in serum PSA.

Adenocarcinoma↗

PubMed2001

Strontium-89 treatment for prostate cancer bone metastases: does a prostate-specific antigen response predict for improved survival?

A review of 50 patients treated with strontium-89 for prostate cancer bone metastases from January 1993-1997 at the Wellington Cancer Centre was undertaken to determine if there was any correlation between changes in prostate-specific antigen (PSA) following treatment and subsequent survival. Thirty cases were evaluable for PSA response. Of these, 14 had a fall in PSA following strontium-89 treatment, and their mean survival was 641 days. The remaining 16 patients did not demonstrate a post-treatment fall in PSA and their mean survival was 275 days. A difference between these two groups in the time to development of new bone symptoms following treatment was also observed. No significant correlation between pretreatment PSA and PSA response was observed. In conclusion, a PSA response following strontium-89 treatment appears to predict for improved survival in patients with bone metastases from carcinoma of the prostate. Further prospective studies are indicated.

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PubMed2006

Docetaxel, estramustine, and 15-month androgen deprivation for men with prostate-specific antigen progression after definitive local therapy for prostate cancer.

PURPOSE: Androgen-deprivation therapy (ADT) is effective for relapsed prostate cancer, but is rarely curative. The purpose of this trial was to determine the feasibility, toxicity, and prostate-specific antigen (PSA) response of chemotherapy and limited ADT for men with PSA relapse. PATIENTS AND METHODS: Eligible men had an increasing PSA and no metastases after prostatectomy and/or radiation for localized disease. Treatment consisted of four cycles of docetaxel (70 mg/m2) every 21 days and estramustine 280 mg tid on days 1 through 5. After chemotherapy, goserelin acetate and bicalutamide were prescribed for 15 months. RESULTS: Sixty-two patients were enrolled. A complete PSA response (CR) was defined as PSA at or below the assay-specific lower limit. The proportion of patients with CR after chemotherapy, after ADT, and at 1 year after completion of ADT was 53%, 63%, and 36%, respectively. Testosterone was more than 100 ng/dL (median, 250 ng/dL) 1 year after completion of ADT in 97% of patients. Patients with a PSA less than 3.0 ng/mL at enrollment had a significantly longer time to progression (TTP; P = .0004). Of 56 patients who were observed at least 1 year after completion of ADT, 23 (41%) have not experienced progression as of their last follow-up. The median TTP is 34 months from treatment initiation (maximum, 74 months free from progression). CONCLUSION: Chemotherapy plus ADT was feasible for early prostate cancer relapse. Forty-one percent of men who are at least 1 year after completion of ADT with recovered testosterone have not experienced progression. This approach is being tested in a randomized trial with investigation of predictors of response.

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PubMed2000

[Clinical evaluation of low dose glucocorticoid therapy for hormone-refractory prostate cancer].

Fifteen cases with hormone-refractory metastatic carcinoma of the prostate were treated by the combination therapy of LH-RH analogue and low-dose glucocorticoid. Prior treatments of the patients were composed of maximum androgen blockade (MAB) therapy (14 cases) and bilateral orichiectomy (1 case). Nine of 15 cases underwent estramustine based treatment or anti-cancer chemotherapy as the second-line therapy. As a glucocorticoid (steroid) therapy, 1.5 or 2.0 mg of dexamethasone or 10 mg of predonisolone were given for a median period of nine months. Clinical responses were evaluated by the determination of serum PSA, EOD score and QOL scales. PSA responses were classified as CR, PR and PD according to the following categories; CR : PSA level decreased to less than 2 ng/ml, PR : PSA level decreased to less than half values of pretreatment level, PD: 20% or more increased to pretreatment level. PSA responses (CR + PR) were observed in eight of 15 patients for a median period of six months. Responses are seemed to be correlated with the Gleason scores. No apparent improvement on EOD scores by bone scintigraphy was seen, however, definite improvement of bone pain was identified in eight of 11 cases. The steroid therapy was considered as one of the useful treatment choice for patients with hormone-refractory prostate cancer.

Aged↗

PubMed2001

PSA and second-line therapy of hormone refractory prostate carcinoma.

The aim of the present study was to correlate PSA response with subjective response (bone pain and performance status), in patients treated for hormone refractory carcinoma of the prostate. Twenty-four patients were introduced into the study. Median PSA was 198 ng/ml. Symptom score, performance status and PSA were monitored monthly for 3 months and then 3-monthly. Sixteen patients (66%) showed a PSA response (median value 10 ng/ml). In 8 patients (33%) PSA was <4 ng/ml. Eight patients (33%) only had a subjective response. However, 75% of the patients with a PSA value <4 ng/ml had a subjective improvement. On the other hand, subjective response was 25% only in patients in whom PSA value decreased to <50% of the initial value but >4 ng/ml. In conclusion, PSA response is not always related to subjective improvement and does not always implicate a beneficial effect of the therapy for the patient.

Adenocarcinoma↗

PubMed2005

[Prostate cancer: update].

The study of mitotic transduction of the signal showed that overexpression of pAkt and reduction in pERK expression would be associated a biological relapse. For tumors T1-3 N0M0 at the high risk of local relapse after prostatectomy, an immediate radiotherapy compared with a differed radiotherapy (at the time of PSA relapse), showed a significant reduction in the rate of local relapse and an ameliorated progression free survival. The effectiveness of the docetaxel was confirmed in two phase III randomized clinical trials : TAX-327 with 3 arms compared docetaxel every 21 days, docetaxel every 7 days and mitoxantrone. All arms were prednisone-based. An increase in overall survival, PSA progression free survival, PSA response rate and a pain reduction were highlighted in the docetaxel arm every 21 days. Docetaxel obtained at the end of this study the marketing authorization in this indication and became the treatment of reference. The SWOG 99-16 study compared the docetaxel estramustine association with the same arm of reference, mitoxantrone and prednisone, with similar results. The addition of estramustine to the docetaxel seems to improve the PSA response rate and progression free survival, but with a greater embolic toxicity. The addition of an antiangiogenic agent, the thalidomide, to docetaxel, improves progression free survival and overall survival. PSA responses were observed with an inhibitor of the proteasome, the bortezomib, in monotherapy, contrary to the imatinib which in monotherapy didn't have any effectiveness. Studies in association with docetaxel are ongoing. Some biological responses were observed with a vaccine anti MUC-1 and must be confirmed on a greater series of patients. The docetaxel impact on localized disease is actually evaluated.

Androgen Antagonists↗

PubMed2004

Combination of LHRH analog with somatostatin analog and dexamethasone versus chemotherapy in hormone-refractory prostate cancer: a randomized phase II study.

OBJECTIVES: To evaluate prospectively the combination of a luteinizing hormone-releasing hormone analog with a somatostatin analog and dexamethasone in patients with hormone-refractory prostate cancer (HRPC) in a randomized Phase II study. HRPC presents a challenging therapeutic problem. Salvage chemotherapy is the usual approach at this stage of the disease. The combination of a luteinizing hormone-releasing hormone analog with a somatostatin analog and dexamethasone has produced objective clinical responses in HRPC. METHODS: Forty patients with HRPC were randomized to receive one of two treatments. Group 1 underwent chemotherapy (estramustine 140 mg three times daily and etoposide 100 mg orally for 21 days) and group 2 the combination of a somatostatin analog (lanreotide 30 mg intramuscularly every 14 days) and dexamethasone (4 mg tapered to 1 mg), in addition to androgen ablation by orchiectomy or a luteinizing hormone-releasing hormone analog (triptorelin 3.75 mg intramuscularly every 28 days). The clinical and prostate-specific antigen (PSA) response, overall survival, time to progression, and toxicity were compared between the two groups. RESULTS: The data of 20 patients in group 1 and 18 in group 2 were analyzed. The demographic and clinical data were similar in the two groups at study entry. A PSA response (decrease of greater than 50%) was observed in 45% of group 1 and 44% of group 2. The difference was not statistically significant. A partial clinical response was observed in 29% and 30% of groups 1 and 2, respectively. Again, the difference was not statistically significant. Changes in performance status and pain score during treatment were not significantly different in the two groups. Hematologic toxicity was more frequent in group 1 (80% of patients), and mild diabetes was more frequent in group 2 (22% of patients). The overall survival was 18.8 months in group 1 and 18 months in group 2 (not statistically significant). The time to progression was 6 versus 4 months and, in the PSA responder subgroup, it was 8 versus 7.7 months in groups 1 and 2, respectively (neither difference was statistically significant). CONCLUSIONS: The results of our randomized Phase II study indicated that the new combination treatment (luteinizing hormone-releasing hormone analog, somatostatin analog, and dexamethasone) may be equally effective as salvage chemotherapy in patients with HRPC in terms of the clinical and PSA response, overall survival, and time to progression. A larger prospective Phase III trial is required to confirm our observations.

Adenocarcinoma↗

PubMed2003

The use of flutamide as a single antiandrogen treatment for hormone-refractory prostate cancer.

OBJECTIVE: To investigate the efficacy of low-dose flutamide (125 mg twice daily) in the treatment of prostate-specific antigen (PSA) recurrence after definitive treatment with radical retropubic prostatectomy (RRP), external-beam radiation therapy (RT), or cryotherapy. PATIENTS AND METHODS: In this phase II prospective trial, patients who had a PSA recurrence after definitive treatment for prostate cancer were treated with flutamide. Endpoints for assessing treatment efficacy were PSA progression, treatment toxicity and clinical symptoms. Results were stratified into complete response (PSA < 0.2 ng/mL on two consecutive assessments), partial response (PSA decrease of half that at baseline on two consecutive assessments) and progressive disease. Seventeen patients were enrolled in who definitive treatment for primary prostate cancer had failed. RESULTS: Low-dose flutamide was clinically effective (i.e. complete or partial response) in 13 patients. Four had a complete response (mean duration 28 months), nine a partial response (mean duration 19 months), and two progressive disease, but were in the study for a mean of 1 year before progression. Two patients discontinued the study at 3 months, secondary to drug-related toxicity; one had grade 3 toxicity and five grade 1 toxicity. CONCLUSIONS: The administration of low-dose flutamide (125 mg) was clinically effective in treating PSA recurrence after definitive treatments for prostate cancer, and was well tolerated. Further investigation in a phase III trial is warranted.

Adult↗

PubMed2003

Weekly high-dose calcitriol and docetaxel in metastatic androgen-independent prostate cancer.

PURPOSE: To determine the safety and efficacy of weekly high-dose oral calcitriol (Rocaltrol, Roche Pharmaceuticals, Basel, Switzerland) and docetaxel (Taxotere, Aventis Pharmaceuticals, Bridgewater, NJ) in patients with metastatic androgen-independent prostate cancer (AIPC). PATIENTS AND METHODS: Thirty-seven patients were treated with oral calcitriol (0.5 micro g/kg) on day 1 followed by docetaxel (36 mg/m(2)) on day 2, repeated weekly for 6 weeks of an 8-week cycle. Patients maintained a reduced calcium diet and increased oral hydration. Prostate-specific antigen (PSA) response was the primary end point, which was defined as a 50% reduction in PSA level confirmed 4 weeks later. RESULTS: Thirty of 37 patients (81%; 95% confidence interval [CI], 68% to 94%) achieved a PSA response. Twenty-two patients (59%; 95% CI, 43% to 75%) had a confirmed > 75% reduction in PSA. Eight of the 15 patients with measurable disease (53%; 95% CI, 27% to 79%) had a confirmed partial response. Median time to progression was 11.4 months (95% CI, 8.7 to 14 months), and median survival was 19.5 months (95% CI, 15.3 months to incalculable). Overall survival at 1 year was 89% (95% CI, 74% to 95%). Treatment-related toxicity was generally similar to that expected with single-agent docetaxel. Pharmacokinetics of either calcitriol or docetaxel were not affected by the presence of its companion drug in an exploratory substudy. CONCLUSION: The combination of weekly oral high-dose calcitriol and weekly docetaxel is a well-tolerated regimen for AIPC. PSA and measurable disease response rates as well as time to progression and survival are promising when compared with contemporary phase II studies of single-agent docetaxel in AIPC. Further study of this regimen is warranted.

Aged↗

PubMed2005

Weekly docetaxel and zoledronic acid every 4 weeks in hormone-refractory prostate cancer patients.

OBJECTIVES: To investigate the safety and efficacy of docetaxel and zoledronic acid in patients with hormone-refractory prostate cancer (HRPC), based on preclinical evidence of synergism between taxanes and bisphosphonates. METHODS: Twenty-five patients with advanced HRPC received weekly docetaxel 30 mg/m2: in 18 patients with symptomatic bone metastases and normal renal function, docetaxel was combined with zoledronic acid, 4 mg i.v. every 4 weeks. Premedication consisted of intravenous dexamethasone before docetaxel. No oral steroids were given. RESULTS: Overall, 12 patients (48%) had a PSA response (reduction of 50% or more compared to baseline). A PSA response was achieved in 8/18 patients (44%) receiving concomitant docetaxel and zoledronic acid, and in 7/12 patients (58%) receiving docetaxel and zoledronic acid as first-line therapy. The weekly schedule of docetaxel resulted in a mean received dose intensity of 26 mg/m2/week, or 87% of the planned dose intensity. Toxicity was mild and as expected for docetaxel. The median time to progression was 7 months, and the median overall survival was 16 months. CONCLUSIONS: Concomitant treatment with docetaxel and zoledronic acid is safe and has encouraging activity in HRPC. The combination should be evaluated in randomised clinical trials.

Aged↗

PubMed2005

Prognostic significance of baseline reverse transcriptase-PCR for prostate-specific antigen in men with hormone-refractory prostate cancer treated with chemotherapy.

PURPOSE: Methods accurately categorizing the diverse biology of prostate cancer are needed. A positive baseline reverse transcriptase-PCR for prostate-specific antigen (RT-PCR PSA) in the androgen-independent setting is an independent prognostic marker of survival. The objectives of the current study were to examine the prognostic implication of baseline RT-PCR PSA positivity during treatment with an active chemotherapeutic agent and explore whether an RT-PCR PSA "response" provides prognostic information. MATERIALS AND METHODS: In a combined analysis of a phase I and a randomized phase II trial of BMS-247550 (an epothilone B analogue), 104 patients with hormone-refractory prostate cancer had whole blood samples collected at baseline, then with each cycle of therapy. RT-PCR PSA was assessed and related to time to progression (TTP). RESULTS: From 100 evaluable patients, 368 samples were received, of which 90.8% were evaluable for RT-PCR PSA status. Baseline RT-PCR PSA status was significantly associated with TTP (hazard ratio, 2.22; 95% confidence interval, 1.40-3.52). Twenty-six of 38 patients positive at first assessment had at least one follow-up RT-PCR PSA that was negative ("response"). In univariate analysis, RT-PCR PSA response was not significantly associated with TTP, but in multivariate analysis, RT-PCR PSA response was of borderline statistical significance in predicting TTP (hazard ratio, 0.41; 95% confidence interval, 0.16-1.01). CONCLUSION: These results provide further confirmation that baseline RT-PCR PSA is a statistically significant predictor of TTP in hormone-refractory prostate cancer. Moreover, this is the first report to suggest that RT-PCR PSA response during chemotherapy treatment may predict TTP.

Adult↗

PubMed2001

Orchidectomy following failure of antiandrogen monotherapy in patients with metastatic prostate cancer.

OBJECTIVE: Patients with metastatic prostate cancer who are initially treated by oral antiandrogens and then have progressive disease may be offered surgical castration as a second-line treatment. Twenty-eight such patients were reviewed to determine the outcome in terms of secondary PSA response, symptomatic relief and disease-specific survival. MATERIALS AND METHODS: Retrospective chart-based review of patients undergoing bilateral scrotal orchidectomy after failure of antiandrogen monotherapy. RESULTS: Patients who had a >50% reduction in PSA at 12 weeks' postorchidectomy had significantly greater duration of PSA response and disease-specific survival. 64% of patients who had bone pain prior to orchidectomy had some relief of symptoms postoperatively. No prognostic indicators of improved survival were identified. CONCLUSION: Orchidectomy as a secondary hormonal treatment following relapse on antiandrogens does produce a response in terms of PSA level and symptoms in some patients.

Aged↗

PubMed2003

Docetaxel-ifosfamide combination chemotherapy in patients with metastatic hormone-refractory prostate cancer: a phase I pharmacokinetic study.

This phase I study was designed to evaluate the activity toxicity and pharmacokinetics of docetaxel combined with ifosfamide in the treatment of hormone-refractory prostate cancer. Ten patients received a median of 4.6 treatment cycles. Docetaxel was administered at a dose of 40 mg/m2 in a 1-hour infusion followed by ifosfamide 3,000 mg/m2 in a 24-hour infusion every 3 weeks. The optimal sequence of chemotherapeutic agents was investigated by reversing the order of administration in the second cycle and by collecting a total of six pharmacokinetic blood samples per cycle from all patients during the first and second cycles. The sequence of administration did not influence the pharmacokinetics of docetaxel. Prostate-specific antigen (PSA) responses were observed in four out of nine patients, with a PSA response rate of 44.4% (complete response + partial response). The treatment was well tolerated. No grade IV toxicities were recorded and grade III leucopenia resulted in dose-reductions in 6 cycles (13.3%). The pharmacokinetic parameters of docetaxel were similar in both sequences. Our recommendation for further phase II studies is ifosfamide followed by low-dose docetaxel. Further phase II efficacy studies are warranted.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2005

[Prognostic factors for PSA relapse of prostate cancer after endocrine therapy].

PURPOSE: Advanced prostate cancer responds well to endocrine therapy initially, but soon becomes refractory and has a poor prognosis. We analyzed the prognostic factors of prostate cancer responding well initially to endocrine therapy with lowering of serum prostate specific antigen (PSA) level but later showing PSA relapse. MATERIALS AND METHODS: In prostate cancer patients newly diagnosed from January 1992 to December 2004 at our institution, there were 93 patients in that the PSA level of 10 ng/ml or more before therapy initially dropped below 10 ng/ml by endocrine therapy, but showed PSA relapse thereafter. We investigated the relationship between clinical stage, pathological differentiation, initial PSA, duration between initiation of therapy and PSA nadir, the value of PSA nadir, duration between initiation of therapy and PSA relapse, PSA doubling time (PSA-DT) at relapse, PSA response three months after initiation of second line therapy and prognosis after PSA relapse. RESULTS: In Kaplan-Meier method, between all or some categories investigated showed significant difference in prognosis after PSA relapse. In multivariate analysis, the factors that significantly affected prognosis after PSA relapse were clinical stage, pathological differentiation, PSA nadir value, duration between initiation of therapy and PSA relapse and PSA response three months after initiation of second line therapy. CONCLUSION: We investigated the prognostic factors refractory to endocrine therapy. These results are useful in planning the therapy, and in explaining the status or future prospective of the disease to patients and families.

Aged↗

PubMed2003

The pattern of prostate-specific antigen responses following hormonal therapy in Thai men with bone metastatic prostate cancer.

OBJECTIVE: To study the pattern of prostate-specific antigen (PSA) responses and prognostic factors following hormonal therapy in Thai men with bone metastatic prostate cancer. MATERIAL AND METHOD: Forty-four patients with bone metastatic prostate cancer treated by bilateral orchiectomy were retrospectively studied for PSA responses during follow-up. The endpoint was time to PSA biochemical failure. PSA pattern and the prognostic factors were evaluated. RESULTS: PSA levels regressed to PSA nadir level in all patients. Time to 50 per cent PSA regression, time to PSA nadir level and time to biochemical failure were 2.1, 6.7 and 11.2 months, respectively. While biochemical failure was present, all patients were alive and had stable clinical conditions. Tumor grading was an important prognostic factor while age and pretreatment PSA level were not a significant indicator. Times to biochemical failure in the patients with well, moderate and poor differentiated tumors were 19.3, 10.0 and 9.3 months, respectively. CONCLUSION: Following bilateral orchiectomy in Thai men with bone metastatic prostate cancer, PSA level decreased continuously to the PSA nadir level in 6-7 months and stable for a period then it increased, known as biochemical failure. The patients with a well differentiated tumor had a significantly longer time to biochemical failure when compared to the patients with a moderate or poor differentiated tumor.

Aged↗

PubMed2003

A phase I study of paclitaxel, estramustine phosphate and vinorelbine (Pacl-E-Vin) in advanced malignancies: triple tubulin targeting.

Anti-tubulin couplets have activity in hormone-resistant prostate cancer. This study was designed to define the dose-limiting toxicity (DLT) and recommended phase II dose (RPTD) of the unique triplet combination of paclitaxel, estramustine phosphate (EMP) and vinorelbine (Pacl-E-Vin). Patients with advanced malignancies who had failed standard therapy, ECOG performance status (PS 0-2) and adequate organ function were included. Dose of EMP was fixed at 300 mg/m2/dose p.o. t.i.d. on days 1-3 and 8-10. Vinorelbine dose was 20 mg/m2/day i.v. on days 3 and 10. Paclitaxel was dose escalated from 40 to 50 mg/m /day i.v. on days 3 and 10. Cycles were repeated every 3 weeks. Twelve adults (median age 72) were entered on this study. Primary tumors included prostate (n=7), cervix (n=2), melanoma (n=1), colon (1) and lung with synchronous prostate cancer (n=1). Nine patients had received no prior chemotherapy, one had received a prior regimen and two had received two or more prior regimens. Of four evaluable patients at dose level 1, one patient had grade 3 neutropenia leading to the day 10 dose being withheld. Of five evaluable patients at dose level 2, there was one DLT (febrile neutropenia) and two grade 3 neutropenias leading to the day 10 dose being withheld. One patient had a lower extremity deep vein thrombosis. Other side effects were mild and reversible. Nine patients were evaluable for efficacy: three with prostate cancer had a greater than 50% prostate-specific antigen (PSA) response, and a patient with synchronous prostate and lung cancer had a greater than 50% PSA response. We conclude that the DLT of Pacl-E-Vin is neutropenia. RPTD is vinorelbine 20 mg/m2, paclitaxel 40 mg/m2, both administered on days 3 and 10, and EMP 900 mg/m2/day on days 1-3 and 8-10, q3w. Dose omission at day 10 followed by 20% dose reduction of paclitaxel and vinorelbine is recommended in the event of grade 3 neutropenia. Activity in hormone-refractory prostate cancer is promising and warrants phase II evaluation.

Adult↗