Treatment of hormone-refractory prostate cancer with docetaxel or mitoxantrone: relationships between prostate-specific antigen, pain, and quality of life response and survival in the TAX-327 study.

PURPOSE: The TAX-327 study randomized 1,006 men with metastatic hormone-refractory prostate cancer to receive 3-weekly docetaxel, weekly docetaxel, or mitoxantrone, each with prednisone. EXPERIMENTAL DESIGN: We used the TAX-327 database to address (a) the relationship between quality of life (QoL) and pain; (b) whether minimally symptomatic patients benefit from treatment or have treatment-related decline in QoL; (c) the relationships between prostate-specific antigen (PSA) response, pain response, and QoL response; (d) the times at which these responses are first observed; and (e) whether PSA, pain, and/or QoL response predict for overall survival. RESULTS: At baseline, 374 of 815 men assessed for QoL had major pain; of these, 92% had substantial impairment of QoL compared with 75% without major pain (P < 0.001). Men with minimal symptoms had prolonged survival (median, 25.6 months) compared with symptomatic patients (median, 17.1 months; P = 0.009); they were more likely to have initial deterioration of QoL if treated with weekly docetaxel. PSA response and pain response, but not QoL response, were independently associated with survival in landmark analysis. Median times to PSA and pain response were 44 and 27 days, respectively; some men had initial increase in serum PSA before subsequent decline. CONCLUSIONS: Symptoms other than pain contribute to impaired QoL in men with hormone-refractory prostate cancer. Those with minimal symptoms have prolonged survival. Both pain and PSA response are associated with survival but are not adequate to use as surrogate end points in phase 3 studies. Early increases in serum PSA (up to 12 weeks) should be ignored when determining response or progression.     

Tolerability and efficacy of docetaxel in older men with metastatic castrate-resistant prostate cancer (mCRPC) in the TAX 327 trial

ObjectiveProstate cancer is a disease of older men. Weekly docetaxel (DPq1w) is often favored over the standard three-weekly regimen (DPq3w) due to concerns about safety and tolerability in this population.Materials and MethodsTwo subgroup analyses of TAX 327 were conducted. Among patients receiving DPq3w, tolerability and efficacy were compared between three age groups: < 65, 65–74 and ≥ 75 years. For men ≥ 75 years, these outcomes were compared between DPq3w, DPq1w, and mitoxantrone (MP) arms. Tolerability outcomes included dose delivery, grade 3/4 adverse events and quality of life. Efficacy outcomes included overall survival and tumor response.ResultsOf 1006 men with metastatic castrate-resistant prostate cancer (mCRPC) in the trial, 335 received DPq3w. Among these, 20% were age ≥ 75 years. For DPq3w, there were non-significant associations of worse tolerability and efficacy with advancing age. Twenty-eight percent of men age ≥ 75 years had an objective pain response, compared to 38% and 34% of patients 65–74 and < 65 years, respectively. There were no significant differences in prostate-specific antigen (PSA) response (43–48%, p = 0.74) or measurable tumor response (7–17%, p = 0.30) according to age. Among men ≥ 75 years, DPq3w resulted in more dose reductions than DPq1w (22% versus 8%, p = 0.007), but tolerability was otherwise comparable. Both were associated with more favorable efficacy than mitoxantrone.ConclusionsTolerability and efficacy of DPq3w appear less favorable with advancing age. Compared to DPq1w, DPq3w is associated with better survival outcomes, but similar tolerability, and remains the standard first-line chemotherapy option in mCRPC. Toxicity is substantial, therefore careful patient selection, close monitoring and early management of toxicities is advised.     

Predictors of tumor response and downstaging in patients who receive preoperative chemoradiation for rectal cancer

BACKGROUND: The objective of this study was to identify predictive factors for pathologic complete response and tumor downstaging after preoperative chemoradiation for rectal cancer. METHODS: Between 1989 and 2004, 562 patients with nonmetastatic rectal adenocarcinoma received preoperative chemoradiation and underwent mesorectal excision. The median radiation dose was 45 Gray (Gy) (range, 19.8-58.6 Gy), 77% of patients received concurrent infusional 5-fluorouracil, 20% of patients received concurrent capecitabine, and 3% of patients received other regimens. RESULTS: Nineteen percent of patients achieved a pathologic complete response (CR), whereas 20% of patients had only microscopic residual disease at surgery, and 61% of patients had macroscopic residual disease at surgery. Downstaging of the tumor stage occurred in 57% of patients. The results from a univariate analysis indicated that tumor circumferential extent>60% (P=.033) and pretreatment carcinoembryonic antigen (CEA) level>2.5 ng/mL (P=.015) were associated significantly with lower pathologic CR rates. The univariate analysis also indicated that tumor circumferential extent>60% (P=.001), pretreatment CEA level>2.5 ng/mL (P=.006), and distance from the anal verge>5 cm (P=.035) were associated significantly with lower downstaging rates. The results from a multivariate logistic regression analysis indicated that greater circumferential extent of tumor (odds ratio [OR], 0.43; P=.033) independently predicted a lower pathologic CR rate. The multivariate logistic regression analysis also indicated that greater circumferential extent of tumor (OR, 0.49; P=.020) and greater distance from the anal verge (OR, 0.46; P=.010) independently predicted a lower downstaging rate. CONCLUSIONS: Circumferential extent of tumor, CEA level, and distance from the anal verge predicted for the pathologic response to preoperative chemoradiation for patients with rectal cancer. Therefore, these factors may be used to predict outcomes for patients, to develop risk-adapted treatment strategies, and to target patients who participate in trials of newer therapies.     

Sequential treatment of metastatic breast cancer with tamoxifen after megestrol acetate therapy and vice versa (a retrospective study)

The progestin megestrol acetate and the anti-estrogen tamoxifen are used as effective drugs in the treatment of metastatic breast cancer and have few side effects. The sequence and indications for use in practice still need to be defined. Of 219 postmenopausal patients with metastatic breast cancer and measurable lesions, 136 were treated with megestrol acetate (MA) per os (180 mg daily) and followed by tamoxifen (TAM) (40 mg daily) in cases with progression, and 83 patients were treated with the inverse drug regimen. In the first line treatment they showed similar effects: MA caused remission in 31/136 patients (23%) and TAM in 17/80 patients (22%) (mean duration 12 and 13 months respectively), while as a second treatment line MA caused remission in 14/83 patients (17%) and TAM in 12/132 patients (9%), which was not significant (P = 0.10). Also with respect to survival there was no significant difference between the two treatment modalities.     

Randomized phase II exploratory study of prophylactic amifostine in cancer patients who receive radical radiotherapy to the pelvis

Background

This study aimed to investigate the efficacy of prophylactic amifostine in reducing the risk of severe radiation colitis in cancer patients receiving radical radiotherapy to the pelvis.

Methods

Patients with pelvic tumours referred for radical radiotherapy who consented participation in this trial, were randomly assigned to receive daily amifostine (A) (subcutaneously, 500 mg flat dose) before radiotherapy or radiotherapy alone (R). Sigmoidoscopy and blinded biopsies were scheduled to conduct prior to initiation and following completion of radiotherapy and again 6 to 9 months later. Radiation colitis was assessed by clinical, endoscopic and histolopathological criteria.

Results

A total 44 patients were enrolled in this trial, the majority with rectal (20 patients) and cervical cancer (12 patients) and were assigned 23 in R arm and 21 in the A arm. In total 119 sigmoidoscopies were performed and 18 patients (18/44, 40.9%) were diagnosed with radiation colitis (15 grade 1 and 2, and 3 grade 3 and 4). Of them, 6 patients belonged to the A group (6/21, 28.6%) and 12 to the R group (12/23, 52.2%). Acute and grade IV radiation colitis was only developed in four patients (17.4%) in the R group. Amifostine side effects were mild. Amifostine treated patients were less likely to develop histologically detectable mucosal lesions, which indicate protection from acute mucosal injury.

Conclusions

Amifostine given subcutaneously can lower the risk of acute severe radiation colitis in patients who receive radical radiotherapy to pelvic tumors.     

Predictor of response to salvage radiotherapy in patients with PSA recurrence after radical prostatectomy: the usefulness of PSA doubling time

BACKGROUND: We assessed predictors of response to salvage radiotherapy (sRT) in patients with prostate-specific antigen (PSA) recurrence after radical prostatectomy. METHODS: A total of 21 patients receiving sRT for PSA recurrence without systemic progression after radical prostatectomy had medical records available for retrospective review. We defined sRT as external beam radiotherapy for patients with a continuous increase in PSA level > or =0.2 ng/ml after radical prostatectomy. Response was defined as achievement of a PSA nadir of < or =0.1 ng/ml. Various pre-treatment parameters were evaluated retrospectively. RESULTS: The median follow-up period after sRT was 38 months. Of the 21 patients, 15 were good responders (71%). The only predictive factor was PSA doubling time (PSADT). Age and PSA level at diagnosis, Gleason score and surgical margin status were not significant predictors of response. The median PSADT in responders was 6.2 months versus 1.9 months in non-responders (P = 0.019). The patients with a PSADT of > or =5 months were all responders. CONCLUSION: PSADT appears to be a good predictor of response to sRT. sRT was especially effective when PSADT was > or =5 months.     

Phase I study of weekly mitoxantrone and docetaxel before prostatectomy in patients with high-risk localized prostate cancer.

PURPOSE: The purpose is to determine the dose-limiting toxicity (DLT) and maximum-tolerated dose (MTD) of mitoxantrone and docetaxel administered weekly before prostatectomy in men with localized prostate cancer at high risk for recurrence. EXPERIMENTAL DESIGN: Twenty-two patients were treated with four cycles of docetaxel 35 mg/m(2) and increasing doses of mitoxantrone starting at 2 mg/m(2) repeated weekly for 3 weeks of a 4-week cycle before prostatectomy. The MTD was defined as that dose at which fewer than one-third of patients experienced a DLT (>or=grade 4 hematological or >or=>grade 3 nonhematological toxicity). Changes in serum prostate-specific antigen and serum testosterone, and pathological outcome with surgery were secondary endpoints. RESULTS: The MTD for mitoxantrone in combination with this dose of docetaxel was 4 mg/m(2). Neutropenia was the DLT for the combination. Ten of 12 patients treated at the MTD completed the planned 16 weeks of chemotherapy, whereas 2 discontinued therapy early because of toxicity. The median reduction in PSA was 41% (range, 4-88%). Serum testosterone levels remained constant postchemotherapy. CONCLUSIONS: In this patient population, the planned Phase II regimen is 4 mg/m(2) mitoxantrone and 35 mg/m(2) docetaxel weekly for 3 of every 4 weeks. Delivery of this regimen before prostatectomy is feasible with acceptable toxicity. Additional studies are needed to determine whether this combined modality approach will reduce cancer recurrence rates in this high-risk population. Because extent of disease and exposure to prior therapy may impact treatment tolerance these safety data may not be applicable to patients with advanced prostate cancer.     

A retrospective study of docetaxel or paclitaxel in patients with advanced or recurrent esophageal squamous cell carcinoma who previously received fluoropyrimidine- and platinum-based chemotherapy

Introduction

Fluoropyrimidine plus platinum (FP)-based chemotherapy has been widely used as a first-line regimen for advanced or recurrent esophageal cancer, and taxanes have shown efficacy after FP-based chemotherapy, but there is no standard regimen for second-line chemotherapy (SLC). We retrospectively investigated the clinical features of taxane therapy in SLC for esophageal squamous cell carcinoma (ESCC).

Methods

The selection criteria were pathologically proven ESCC; advanced or recurrent disease previously treated with FP at our hospital; performance status (PS) 0–2; and adequate organ function. Docetaxel (DTX) was administered 3-weekly at 70 mg/m². Paclitaxel (PTX) was administered at 100 mg/m² weekly for 6 weeks, with 1 week’s rest.

Results

The analysis covered 163 patients from August 2006 to June 2012. Median age was 64 years (range 37–83: DTX group 132 patients and PTX group 31). Progression-free survival and median overall survival (OS) were 2.3 and 6.1 months, respectively, with PTX and 2.3 and 5.3 months with DTX. Response rates were 20.7 % for PTX and 5.9 % for DTX. The rate of grades 3–4 neutropenia was higher with DTX (32.6 %) than with PTX (16.1 %). Grade 3 febrile neutropenia was seen in 6.1 % of DTX recipients but in no PTX group. According to multivariate analyses of OS, PS 2, number of metastatic sites ≧2, and CRP ≧1 mg/dL were independent predictors of poor prognosis.

Conclusions

PTX and DTX were both effective in SLC for ESCC, but their toxicity profiles differed. In terms of febrile neutropenia, PTX seems more appropriate.     

Dose-escalation study of docetaxel in combination with mitoxantrone as first-line treatment in patients with metastatic breast cancer.

PURPOSE: To define the maximum-tolerated dose (MTD) and the dose-limiting toxicities (DLTs) of docetaxel in combination with mitoxantrone in patients with metastatic breast cancer (MBC). PATIENTS AND METHODS: Forty-one chemotherapy-naive patients with MBC (median age, 61 years) were enrolled. Thirty-eight (93%) had performance status (World Health Organization [WHO]) 0, 29 (71%) were postmenopausal, and 21 (51%) had estrogen receptor-negative tumors. Patients received escalated doses of docetaxel (75 to 100 mg/m2) on day 1 and mitoxantrone (8 to 22 mg/m2) on day 8. Treatment was repeated every 3 weeks. RESULTS: A total of 217 chemotherapy cycles were administered. Without recombinant human granulocyte colony-stimulating factor (rhG-CSF) support, the MTD1 occurred at the first dose level (docetaxel 75 mg/m2 and mitoxantrone 8 mg/m2); DLTs were febrile neutropenia, grade 4 neutropenia lasting more than 5 days, and grade 3 diarrhea. With prophylactic rhG-CSF, the MTD2 was docetaxel 100 mg/m2 and mitoxantrone 20 mg/m2; DLTs were febrile neutropenia and grade 4 neutropenia. Nine (22%) patients developed neutropenia after the first cycle of treatment. A total of 19 episodes of febrile neutropenia (9% of the cycles) occurred during the whole period of the study; there were no toxic deaths. At high docetaxel (100 mg/m2) and mitoxantrone (> 12 mg/m2) dose levels, a significant decrease of the absolute lymphocyte number was observed; immunophenotyping revealed that all lymphocyte subpopulations were reduced. Grades 2 and 3 neurosensory toxicity occurred in six patients (15%) and one patient (2%), respectively. No cardiac toxicity was observed. Nine complete responses (22%) and 23 partial responses (56%) were achieved (overall response rate, 78%; 95% confidence interval, 62.5% to 88.8%). The median duration of response was 12.5 months, and the median time to tumor progression was 14.5 months. CONCLUSION: The reported combination of docetaxel and mitoxantrone with G-CSF support is a safe, intensified, well-tolerated, and effective regimen as first-line treatment in patients with MBC.     

Impact of the number of treatment courses on the clinical response of patients who receive high-dose bolus interleukin-2.

PURPOSE: To determine the impact of treatment with successive courses of high-dose bolus interleukin-2 (IL-2) on the incidence of clinical responses in patients with metastatic melanoma or renal cell cancer. PATIENTS AND METHODS: A consecutive series of 350 patients with either metastatic melanoma or renal cell cancer who were treated with high-dose bolus IL-2 in the Surgery Branch, National Cancer Institute, between September 1985 and November 1996 was analyzed, with a median potential follow-up of 7.1 years. All patients were treated with 720,000 IU/kg of IL-2 administered by a 15-minute intravenous infusion every 8 hours for up to 5 days, as clinically tolerated per cycle. Patients were retreated according to clinical response and tolerance to the IL-2 therapy. RESULTS: Of the 149 patients with melanoma, 10 achieved complete responses (CRs) and 13 partial responses (PRs), for an overall response rate of 15.4%. Of the 201 patients with renal cell cancer, 18 achieved CRs and 20 PRs, for an overall response rate of 19.0%. Among responding patients, 21 of 23 with melanoma and 34 of 38 with renal cell cancer developed at least PRs after the first course of IL-2. CONCLUSION: Most patients with metastatic melanoma and renal cell cancer who achieved PRs or CRs to intravenous high-dose bolus IL-2 were identified after the first course of therapy. Those who demonstrated no response after two treatment courses failed to respond to additional IL-2 therapy. Based on this retrospective analysis, we recommend that patients who exhibit objective responses to treatment with high-dose bolus IL-2 receive additional treatment courses until either CR or IL-2 intolerance develops. Patients who do not achieve objective responses after two courses of IL-2 should receive no further treatment with this regimen.     

Phase II randomized study of weekly docetaxel alone or plus UFUR treatment in non-small cell lung cancer patients who failed previous chemotherapy

PURPOSE: This study aimed to assess the feasibility and efficacy of adding UFUR (UFT, tegafur/uracil) into weekly docetaxel treatment for non-small cell lung cancer (NSCLC) patients who failed previous platinum-based chemotherapy. METHODS: Patients were randomized into two arms: docetaxel 40mg/m(2) intravenous infusion (IV) on days 1 and 8 of every 3 weeks (arm D), and docetaxel 35mg/m(2) IV on days 1 and 8 plus daily oral UFUR 150mg/m(2) of every 3 weeks (arm DU), with arm D as a control arm. Treatment was given to a maximum of 6 cycles and carried out in the outpatient clinic. RESULTS: From January 2005 to March 2006, 48 patients were enrolled and randomized into the study, with 24 patients in each arm. The mean number of cycles of treatment was 4 in the D arm and 3.5 in the DU arm. Objective response rates were 29.2% in the D arm and 8.3% in the DU arm (p=0.067). Toxicities were few and mild in degree in both arms. Median time to disease progression was 4.5 months in the D arm and 2.1 months in the DU arm (p=0.4682). Median survival time was 10.9 months in the D arm and 15.2 months in the DU arm (p=0.8442). CONCLUSIONS: The addition of UFUR to weekly docetaxel treatment did not improve response rate and time to disease progression in NSCLC patients who failed previous platinum-based chemotherapy.     

Clinical outcome in gastrointestinal stromal tumor patients who interrupted imatinib after achieving stable disease or better response

BACKGROUND: Imatinib has been found to be effective in the treatment of patients with gastrointestinal stromal tumors (GIST). We sought to evaluate the clinical outcome of imatinib interruption in GIST patients who had achieved stable disease (SD) or showed better response to imatinib therapy. METHODS: From July 2001 to December 2004, we prospectively collected clinical data from 62 consecutive patients with advanced GIST, of whom 58 (93.5%) achieved SD or better response to imatinib therapy and were included in this study. Imatinib therapy was interrupted in 14 of the 58 patients (interruption group, INT), after a median time of 11.9 months. Progression-free survival (PFS) after imatinib interruption was calculated and imatinib-refractory PFS and overall survival (OS) were compared between the INT group and the 44 patients who continued imatinib treatment (continuation group, CONT). RESULTS: After a median follow-up of 17.9 months following imatinib interruption, nine patients (64%) had progressive disease (PD) with a median PFS from the date of imatinib interruption of 10.0 months. Median PFS dated from the time of imatinib initiation in the INT group was 21.8 months (95% CI, 17.3-26.3 months), but was not reached in the CONT group (P=0.029). Following imatinib reintroduction in the INT group, 88% of patients achieved disease control. There were no statistically significant differences in imatinib-refractory PFS (P=0.405) and OS (P=0.498) between the groups. CONCLUSION: In GIST patients controlled with imatinib, treatment might be interrupted, at least temporarily, when clinically warranted.     

Pharmacologic and phenotypic study of docetaxel in patients with ovarian or primary peritoneal cancer

Purpose

The objectives of this study were to determine whether the midazolam clearance predicted docetaxel pharmacokinetics, CA-125 change, and response and to assess the impact of cytochrome P450 (CYP) 3A5 and ATP-binding cassette, subfamily B, member 1 (ABCB1) genotypes on docetaxel pharmacokinetics and pharmacodynamics in ovarian or primary peritoneal cancer patients.

Methods

Thirty-four patients with advanced ovarian and primary peritoneal cancer were administered docetaxel at 75?mg/m² as a 1-h infusion in combination with carboplatin IV over 30?min at a target AUC of 5?mg/ml?min. Cycles were repeated every 21?days for 6 cycles. Midazolam was administered at 2?mg as a 30-min IV infusion the day prior to cycle one of docetaxel administration. Pharmacokinetic studies of docetaxel and CYP3A5 and ABCB1 genotype studies were performed.

Results

There was an inverse relationship between midazolam clearance (CL) and CA-125 level after cycle 6 where a higher midazolam CL was associated with a CA-125?<10?U/ml (P?=?0.007) and CA-125?<15?U/ml (P?=?0.048). The CA-125 categories were associated with response achieved (complete response/partial response) (CR/PR), stable disease (SD), and progressive disease (PD) at the end of therapy (P?=?0.0173). Docetaxel CL was not related to midazolam CL or genotype. Docetaxel exposure and genotypes were not related to toxicity or response (P?>?0.05).

Conclusions

The midazolam CL predicted CA-125 levels and response that was independent of other factors including docetaxel pharmacokinetics. Future studies need to evaluate the mechanism for the relationship between midazolam CL and response in patients with ovarian cancer.     

A phase 2 study of carboplatin plus docetaxel in men with metastatic hormone-refractory prostate cancer who are refractory to docetaxel

BACKGROUND: Prostate cancer is the second leading cause of cancer mortality among men in the U.S. To the authors' knowledge, there is no proven, effective, second-line therapy for docetaxel-refractory disease. Recent data suggest that platinum salts may be effective when combined with taxanes in metastatic hormone-refractory prostate cancer (HRPC). The authors conducted a phase 2 trial of docetaxel plus carboplatin chemotherapy in this disease setting. METHODS: Eligible men had metastatic HRPC that had progressed during or within 45 days after the completion of docetaxel-based chemotherapy. Patients were treated with intravenous docetaxel at a dose of 60 mg/m(2) plus carboplatin at an area under the curve of 4 once every 21 days until they had either disease progression or unacceptable toxicity. RESULTS: Thirty-four patients were enrolled. Therapy was tolerated reasonably well; Grade 3 leukopenia (graded according to the Common Toxicity Criteria grading system) was the most common adverse event (experienced by 56% of patients), but there was only 1 episode of febrile neutropenia reported. Prostate-specific antigen (PSA) declines > or =50% were noted in 18% of patients, and measurable responses were observed in 14%. The median duration of PSA response was 5.7 months. The median progression-free survival was 3 months, and the median overall survival was 12.4 months. Patients were more likely to respond to the combination if they previously had responded to docetaxel. CONCLUSIONS: In men with HRPC who developed progressive disease during or shortly after treatment with docetaxel, the addition of carboplatin resulted in modest additional activity. Taxane-refractory HRPC is an area of unmet need, and the current trial has provided evidence that platinum chemotherapy may be an important therapeutic option.     

Phase II study of docetaxel in patients with relapsed or refractory malignant lymphoma

We report the activity and toxicity of docetaxel in 12 evaluable heavily pretreated patients with relapsed and refractory non-Hodgkin's lymphoma and Hodgkin's disease. In all, 42% achieved a partial response, 25% achieved stable disease. Median duration of response was 16 (10-21) weeks. The median overall survival was 70 (9-178) weeks and for responders it was 120 (22-178) weeks. One patient developed one episode of neutropenic sepsis. Docetaxel has limited activity in this group of patients.     

Phase II study of docetaxel and capecitabine in patients with metastatic or recurrent gastric cancer

OBJECTIVES: A phase II study was conducted to evaluate the response rate and safety of a combination regimen of docetaxel plus capecitabine in patients with advanced gastric cancer. PATIENTS AND METHODS: Patients with previously untreated metastatic or recurrent measurable gastric cancer received i.v. docetaxel 75 mg/m2 on day 1 and oral capecitabine 1,000 mg/m2 twice daily from day 1 to 14 every 3-week cycle. RESULTS: Thirty-two patients were enrolled in the current study. Of these, 30 patients were assessable for efficacy and 31 assessable for toxicity. One complete response and 13 partial responses were confirmed, giving an overall response rate of 43.8% (95% CI; 25.6-61.9%). The median time to progression and median overall survival for all patients was 5.07 months and 8.4 months, respectively. Grade 3/4 neutropenia occurred in 3 patients (9.7%) and febrile neutropenia was observed in 2 patients (6.3%). Grade 1/2 nausea was observed in 45.2% of patients. Grade 2-3 hand-foot syndrome occurred in 4 patients (12.9%). CONCLUSIONS: The combination of docetaxel and capectabine was found to be well tolerated and effective in patients with advanced gastric cancer. Accordingly, this regimen can be regarded as an important first-line treatment option for advanced gastric cancer.     

Phase I study of docetaxel and cyclophosphamide in patients with advanced or recurrent breast cancer

BACKGROUND: A phase I clinical study of combination chemotherapy with docetaxel and cyclophosphamide (CPA) was performed to determine the maximum tolerated dose (MTD), the incidence and severity of toxicities and the pharmacokinetics in patients with advanced or recurrent breast cancer. METHODS: Docetaxel was administered by intravenous drip infusion over 60 minutes, followed by intravenous bolus injection of CPA every 3-4 weeks. The dosage of docetaxel/CPA was 40/200, 40/400, 50/400, or 60/400 mg/m(2)/day. RESULTS: Fifteen patients were enrolled and received a total of 33 cycles of the combined therapy. The dose limiting toxicities (DLTs) were leukopenia, neutropenia and thrombocytopenia. The MTD was estimated to be docetaxel 60 mg/m(2) in combination with CPA 400 mg/m(2) per day. Plasma clearance of both drugs was similar regardless of dose. The recommended doses of docetaxel/CPA for a phase Utrial are 50/400 mg/m(2)/day every 3-4 weeks. CONCLUSION: The MTD of this combined therapy was docetaxel 60 mg/m(2) and CPA 400 mg/m(2). Neutropenia and leukopeina were common and severe. It is important to stress the need for modification of the dosing scheme.     

A prognostic model in patients who receive chemotherapy for metastatic or recurrent gastric cancer: validation and comparison with previous models

Purpose  

To make up for the limitations of previous prognostic models, we developed and validated a model in patients with metastatic or recurrent gastric adenocarcinoma (AGC), and to compare with previous models.