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Matthew D Galsky

Publications and source records attributed to Matthew D Galsky.

9 recordsLinked to original sources
PubMed2007

Phase II trial of dose-dense doxorubicin plus gemcitabine followed by paclitaxel plus carboplatin in patients with advanced urothelial carcinoma and impaired renal function.

BACKGROUND: Cisplatin-based therapy is standard in patients with advanced urothelial carcinoma but a large proportion are ineligible due to renal impairment. The safety and activity of a dose-dense carboplatin-based regimen in this patient population were explored. METHODS: Patients with advanced urothelial carcinoma who were ineligible for cisplatin were eligible based on at least 1 of the following: 1) serum creatinine >1.5 mg/dL; 2) creatinine clearance of >30 mL/min/1.73 m(2) and <60 mL/min/1.73 m(2); and/or 3) prior nephrectomy. Patients received treatment with doxorubicin plus gemcitabine every other week x 5 cycles followed by paclitaxel plus carboplatin weekly x 12 cycles. RESULTS: Twenty-five patients were treated. Myelosuppression was the major toxicity, with 28% of patients experiencing grade 3-4 neutropenia; there were only 2 (8%) episodes of febrile neutropenia. Grade > or = 3 nonhematologic toxicities were infrequent with the exception of grade > or = 3 thrombotic episodes in 4 (16%) patients. There were 5 complete responses and 9 partial responses for an overall response rate of 56% (95% confidence interval [CI]: 35%-76%). The median survival was 15 months (95% CI: 11-30). At a median follow-up for survivors of 45 months, 7 (28%) patients are disease-free. CONCLUSIONS: Dose-dense sequential chemotherapy is tolerable and active in patients with urothelial carcinoma and renal impairment. Prolonged disease-free survival is achievable in a subset of patients with primary unresectable disease or lymph-node only metastases treated with carboplatin-based therapy +/- surgical consolidation. Randomized trials are needed to define the optimal regimen in patients with advanced urothelial carcinoma and renal impairment.

Adult↗
PubMed2006

Phase II trial of pemetrexed as second-line therapy in patients with metastatic urothelial carcinoma.

PURPOSE: The purpose of this single-center phase II study was to determine the activity of pemetrexed administered as second-line therapy in patients with advanced urothelial carcinoma. METHODS: Patients with advanced urothelial carcinoma that had relapsed after receiving perioperative chemotherapy, or progressed on first-line chemotherapy for metastatic disease, were eligible for enrollment. Patients received pemetrexed 500 mg/m(2) every 21 days along with folic acid and vitamin B12 supplementation. RESULTS: A total of 13 patients were enrolled. An objective response was achieved in 1/12 evaluable patients for an overall response rate of 8% (90% upper limit 29%). This level of activity did not meet criteria for expansion based on the pre-defined optimal 2-stage Simon design and the trial was concluded. Treatment was generally well tolerated, however, 2/13 patients developed febrile neutropenia. Non-hematologic grade > or = 3 toxicity was rare. CONCLUSIONS: Pemetrexed as second-line therapy in advanced urothelial carcinoma is associated with modest activity. The role of this novel antifolate in chemotherapy-naïve patients warrants further investigation.

Administration, Oral↗
PubMed2006

Impact of renal impairment on eligibility for adjuvant cisplatin-based chemotherapy in patients with urothelial carcinoma of the bladder.

BACKGROUND: Perioperative cisplatin-based chemotherapy has shown benefit in patients with high-risk localized urothelial bladder cancer, but it is not widely used. Renal impairment may be a major factor limiting its use. The current study was designed to determine the proportion of patients ineligible to receive adjuvant cisplatin-based chemotherapy based on inadequate renal function alone. METHODS: Patients who underwent radical cystectomy for urothelial cancer of the bladder with evidence of extravesical disease (> or =pT3 or any N+) were identified. Patients who received neoadjuvant chemotherapy were excluded. Serum creatinine immediately before and nadir serum creatinine after cystectomy were used to calculate creatinine clearance (CrCl) or glomerular filtration rate (GFR) using the Cockroft-Gault (CG), Jelliffe, and Modification of Diet in Renal Disease (MDRD) study formulas. A cutoff of CrCl <60 mL/min or GFR <60 mL/min/1.73 m2 was used to determine ineligibility for cisplatin-based chemotherapy. The proportion of patients ineligible by each formula was compared by univariate logistic regression. Univariate linear regression was performed to determine the effect of age on CrCl or GFR. RESULTS: : Most patients were pT3 or greater; 39% were lymph node-positive. The overall proportion of patients ineligible for cisplatin-based chemotherapy was 28% by the CG formula, 52% by Jelliffe, and 24% by MDRD. Concordance between formulas was low. With all formulas the probability of ineligibility increased with age: by the CG equation, >40% of patients age >70 years were ineligible. CONCLUSIONS: : The widespread use of cisplatin-based perioperative chemotherapy in patients with high-risk localized bladder cancer may be significantly limited by the high prevalence of baseline renal insufficiency in this population. This finding is most striking in the elderly. Better selection of patients who may safely receive cisplatin and more effective regimens devoid of cisplatin are required to optimize outcomes in this group of patients.

Age Factors↗
PubMed2006

A retrospective evaluation of second-line chemotherapy response in hormone-refractory prostate carcinoma: second line taxane-based therapy after first-line epothilone-B analog ixabepilone (BMS-247550) therapy.

BACKGROUND: Epothilones and taxanes interfere with microtubule function. Ixabepilone, which is an epothilone-B analog, has activity against taxane-resistant cell lines and as first-line therapy for men with hormone-refractory prostate carcinoma (HRPC). Clinical cross-resistance of ixabepilone and taxanes in HRPC is unknown. METHODS: Records were evaluated retrospectively from patients with HRPC who were treated on a randomized Phase II trial of ixabepilone with or without estramustine and who subsequently received taxane chemotherapy. Posttherapy declines in prostate-specific antigen (PSA) levels and time to PSA progression were defined by consensus criteria. The median survival was evaluated by using the Kaplan-Meier method. RESULTS: Forty-nine patients who received ixabepilone with estramustine (28 patients) or without estramustine (21 patients) subsequently received second-line taxane therapy. Second-line PSA declines > or = 50% were achieved by 51% of patients (95% confidence interval [95% CI], 33-66%). Second-line PSA declines > or = 50% were achieved by 61% of patients (95% CI, 42-78%) who achieved a first-line PSA decline > or = 50% with ixabepilone, compared with 33% of patients (95% CI, 13-59%) who did not (P = 0.08). Patients who discontinued first-line ixabepilone treatment for disease progression were less likely to achieve a PSA decline > or = 50% in response to second-line, taxane-based therapy compared with patients who discontinued for toxicity or patient preference (36% vs. 71%; P = 0.01). CONCLUSIONS: Second-line taxane chemotherapy after ixabepilone resulted in a substantial frequency of PSA declines. Although patients with ixabepilone-refractory disease were less likely to respond to second-line taxane chemotherapy, 36% did achieve a PSA response. These findings were consistent with incomplete clinical cross-resistance between the taxanes and the epothilones.

Aged↗
PubMed2005

Multi-institutional randomized phase II trial of the epothilone B analog ixabepilone (BMS-247550) with or without estramustine phosphate in patients with progressive castrate metastatic prostate cancer.

PURPOSE: To evaluate the antitumor activity and safety of the epothilone B analog, ixabepilone, with or without estramustine phosphate (EMP), in chemotherapy-naive patients with progressive castrate metastatic prostate cancer. PATIENTS AND METHODS: Patients were randomly assigned to receive ixabepilone (35 mg/m(2)) by intravenous infusion every 3 weeks with or without EMP 280 mg orally three times daily on days 1 to 5. RESULTS: Between December 2001 and October 2003, 92 patients were enrolled and randomly assigned to treatment with ixabepilone alone (45 patients) or in combination with EMP (47 patients). Grades 3 and 4 toxicities experienced by more than 5% of patients included neutropenia (22%), fatigue (9%), and neuropathy (13%) on the ixabepilone arm, and neutropenia (29%), febrile neutropenia (9%), fatigue (9%), neuropathy (7%), and thrombosis (6%) on the ixabepilone + EMP arm. Post-treatment declines in prostate-specific antigen of > or = 50% were achieved in 21 of 44 patients (48%; 95% CI, 33% to 64%) on the ixabepilone arm, and 31 of 45 patients (69%; 95% CI, 55% to 82%) on the ixabepilone + EMP arm. In patients with measurable disease, partial responses were observed in eight of 25 patients (32%; 95% CI, 14% to 50%) on the ixabepilone arm, and 11 of 23 (48%; 95% CI, 27% to 68%) on the ixabepilone + EMP arm. Time to prostate-specific antigen progression was 4.4 months (95% CI, 3.1 to 6.9 months) on the ixabepilone-alone arm and 5.2 months (95% CI, 4.5 to 6.8 months) on the combination arm. CONCLUSION: Ixabepilone, with or without estramustine phosphate, is well tolerated and has antitumor activity in patients with castrate metastatic prostate cancer.

Aged↗
PubMedDate not supplied

The role of taxanes in the management of bladder cancer.

Transitional cell carcinoma of the bladder is a chemo-sensitive neoplasm. Whereas the MVAC (methotrexate, vinblastine, doxorubicin, and cisplatin) regimen was long considered the standard of care for patients with advanced disease, the evaluation of newer agents with retained activity and improved tolerability has been the focus of much investigation over the past decade. Among the most important of these newer agents are taxanes. Whereas taxane-containing regimens have not yet been shown to improve the survival of patients with transitional cell carcinoma in randomized trials, ongoing phase III trials will further define the role of these agents in both the perioperative and advanced disease settings.

Antineoplastic Combined Chemotherapy Protocols↗