Gemcitabine in Combination With Doxorubicin in Advanced Breast Cancer: Final Results of a Phase II Pharmacokinetic Trial

2000 ◽  
Vol 18 (13) ◽  
pp. 2545-2552 ◽  
Author(s):  
G. Pérez-Manga ◽  
A. Lluch ◽  
E. Alba ◽  
J.A. Moreno-Nogueira ◽  
M. Palomero ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Phase Ii ◽  
Response Rate ◽  
Single Agent ◽  
Metastatic Breast ◽  
Complete Response ◽  
Breast Disease ◽  
Advanced Breast ◽  
Weekly Schedule

PURPOSE: Gemcitabine has promising single-agent activity in advanced breast disease. The aim of this phase II study was to determine the efficacy, toxicity, and pharmacokinetic profile of gemcitabine administered with doxorubicin as first-line treatment in patients with metastatic breast cancer. PATIENTS AND METHODS: Of the 42 women with metastatic breast cancer (age 33 to 74 years; mean age, 55 years), 13 were chemotherapy-naive and 29 had received adjuvant chemotherapy. Gemcitabine (800 or 1,000 mg/m2) and doxorubicin (25 mg/m2) were administered intravenously on days 1, 8, and 15 of each 28-day cycle. Blood samples were drawn on day 8 of cycles 1, 2, and 3 and of subsequent odd cycles for gemcitabine pharmacokinetic determinations and before and after the first dose of cycle 1 or 2 for doxorubicin determinations. RESULTS: There were three complete and 20 partial responses, for an overall response rate of 55% (95% confidence interval [CI], 40% to 70%) and a complete response rate of 7%. The median survival time for all 42 patients was 27 months (95% CI, 13.4 to 30.0 months) and the 1-year survival rate was 80%. Toxicity was mainly hematologic. The disposition of both drugs was unchanged when they were administered on the same day compared with when they were given singly. CONCLUSION: The combination of gemcitabine (800 mg/m2) and doxorubicin (25 mg/m2) can be safely administered using a weekly schedule. The disposition of both drugs is unchanged when they are administered on the same day. This combination shows promising activity with acceptable toxicity compared with other combination therapies.

Phase II Trial of N,N-Diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine.HCl and Doxorubicin Chemotherapy in Metastatic Breast Cancer: A National Cancer Institute of Canada Clinical Trials Group Study

1999 ◽  
Vol 17 (11) ◽  
pp. 3431-3437 ◽  
Author(s):  
K. Khoo ◽  
L. Brandes ◽  
L. Reyno ◽  
A. Arnold ◽  
S. Dent ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Metastatic Breast Cancer ◽  
Phase Ii ◽  
National Cancer Institute ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Single Agent ◽  
Metastatic Breast ◽  
Phase Iii

PURPOSE: This multicenter phase II trial investigated the efficacy and toxicity of a combination of the novel intracellular histamine antagonist, N,N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine.HCl (DPPE), and doxorubicin in patients with anthracycline-naïve metastatic breast cancer. Preclinical models and early single institutional studies suggested DPPE could potentiate the cytotoxicity of doxorubicin. PATIENTS AND METHODS: Forty-two women, 32 to 77 years old (median, 59 years), with anthracycline-naïve metastatic breast cancer were treated. Patients may have had one previous regimen of nonanthracycline chemotherapy, either in the adjuvant or metastatic disease treatment setting. DPPE (6 mg/kg) was administered as an 80 minute intravenous infusion with doxorubicin (60 mg/m2) given intravenously over the last 20 minutes of the DPPE infusion. Patients were premedicated with an antiemetic and sedating regimen. The DPPE/doxorubicin treatment was given every 21 days for a maximum of seven cycles. RESULTS: All 42 patients were assessable. Overall, toxicity was comparable to that expected with doxorubicin alone, with the exception of DPPE-related motion sickness, mild hallucinations, and cerebellar signs at the time of the infusion. These CNS side effects were manageable in an ambulatory care setting, improved with subsequent cycles of treatment, and did not usually require hospitalization. Four patients developed febrile neutropenia. Thirty-five patients received four or more cycles of chemotherapy. The overall response rate was 52.5% (95% confidence interval, 36% to 68%), with 9.5% complete responses (n = 4), 43% partial responses (n = 18), and 38% of patients with stable disease (n = 16). CONCLUSION: The antitumour effects of DPPE/doxorubicin the 52.5% response rate seems encouraging, particularly in consideration of the fact that a recently reported randomized National Cancer Institute of Canada Clinical Trials Group trial using single-agent doxorubicin 60 mg/m2 in one of the treatment arms achieved a 31% response rate. Thus, a randomized phase III trial of doxorubicin versus doxorubicin plus DPPE is being conducted in this clinical setting.

scholarly journals Phase II Studies of Gemcitabine and Cisplatin in Heavily and Minimally Pretreated Metastatic Breast Cancer

2009 ◽  
Vol 27 (13) ◽  
pp. 2163-2169 ◽  
Author(s):  
Helen K. Chew ◽  
James H. Doroshow ◽  
Paul Frankel ◽  
Kim A. Margolin ◽  
George Somlo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Genetic Polymorphisms ◽  
Phase Ii ◽  
Response Rate ◽  
Single Agent ◽  
Metastatic Breast ◽  
High Dose ◽  
Phase Ii Trials ◽  
Heavily Pretreated

Purpose Cisplatin and gemcitabine have single-agent activity in metastatic breast cancer, and preclinical data support synergy of the combination. Two parallel, phase II trials were conducted to evaluate the response rate, response duration, and toxicities of the combination. Genetic polymorphisms were analyzed for correlation with outcomes. Patients and Methods Eligible women had measurable disease and heavily or minimally pretreated metastatic breast cancer. The heavily pretreated protocol required prior anthracycline and taxane therapy; cisplatin as part of high-dose therapy was allowed. All patients received cisplatin 25 mg/m2 on days 1 through 4 and gemcitabine 1,000 mg/m2 on days 2 and 8 of a 21-day cycle with prophylactic granulocyte colony-stimulating factor in the heavily pretreated group. Sera from a subset of patients were evaluated by polymerase chain reaction restriction fragment length polymorphism for polymorphisms in 10 genes of interest. Results Of 136 women enrolled, 74 were heavily pretreated. Both protocols accrued to their two-stage design. The response rate for both the heavily and minimally pretreated cohorts was 26%, and the median durations of response were 5.3 and 5.9 months, respectively. In a multivariate analysis, hormone receptor–negative disease was associated with a higher response rate. The most common grades 3 or 4 toxicities were thrombocytopenia (71%), neutropenia (66%), and anemia (38%). In a subset of 55 patients, the xeroderma pigmentosum group D (XPD)–751, x-ray cross-complementing group 3 (XRCC3) and cytidine deaminase polymorphisms were significantly associated with clinical outcomes. Conclusion Combination cisplatin and gemcitabine is active in metastatic breast cancer regardless of prior therapy. Genetic polymorphisms may tailor which patients benefit from this regimen.

scholarly journals Phase II Trial of Sorafenib in Patients With Metastatic Breast Cancer Previously Exposed to Anthracyclines or Taxanes: North Central Cancer Treatment Group and Mayo Clinic Trial N0336

2009 ◽  
Vol 27 (1) ◽  
pp. 11-15 ◽  
Author(s):  
Alvaro Moreno-Aspitia ◽  
Roscoe F. Morton ◽  
David W. Hillman ◽  
Wilma L. Lingle ◽  
Kendrith M. Rowland ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Phase Ii ◽  
Single Agent ◽  
Evaluation Criteria ◽  
Metastatic Breast ◽  
Complete Response ◽  
Prior Treatment ◽  
Efficacy Analysis ◽  
Metastatic Setting

PurposeWe conducted a cooperative group phase II study to assess antitumor activity and toxicity of sorafenib in patients with metastatic breast cancer (MBC) who had received prior treatment for their disease.Patient and MethodsPatients were eligible if they had measurable disease and had previously received an anthracycline and/or a taxane in the neoadjuvant, adjuvant, or metastatic setting. The primary end point of the study was tumor response per Response Evaluation Criteria in Solid Tumors (RECIST). The study was designed in two stages. Sorafenib was administered as 400 mg twice daily on days 1 through 28 of each 4-week cycle.ResultsTwenty-three patients were enrolled with a median age of 54 years (range, 37 to 70 years). Twenty-two (96%) had prior anthracycline treatment and 16 (70%) had prior taxane treatment. Patients received sorafenib for a median of two cycles (range, one to 15 cycles) with a median follow-up of 2.4 years (range, 2.2 to 2.6 years). There were no grade 4 toxicities and few grade 3 toxicities. Among the 20 patients eligible for efficacy analysis, no patients experienced a partial response or complete response per RECIST criteria. Thus, the trial stopped at the end of the first stage per study design. Two patients (10%; 90% CI, 1.8% to 28.3%) achieved stable disease lasting longer than 6 months.ConclusionSorafenib as a single agent, although well tolerated, did not exhibit activity when measured by tumor shrinkage in patients with MBC who had received prior treatment. Further research should focus on combinations with standard therapy and end points more sensitive to effects of targeted agents, such as disease stabilization.

Phase II Trial of Doxorubicin and Paclitaxel Plus Granulocyte Colony-Stimulating Factor in Metastatic Breast Cancer: An Eastern Cooperative Oncology Group Study

1999 ◽  
Vol 17 (12) ◽  
pp. 3828-3834 ◽  
Author(s):  
Joseph A. Sparano ◽  
Ping Hu ◽  
Radha M. Rao ◽  
Carla I. Falkson ◽  
Antonio C. Wolff ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Complete Response Rate ◽  
Objective Response ◽  
Metastatic Breast ◽  
Complete Response ◽  
Institutional Setting

PURPOSE: Several groups have reported that the combination of doxorubicin plus paclitaxel given as a 3-hour intravenous (IV) infusion for up to eight cycles produces a high response rate (> 80%) and complete response rate (> 20%) in metastatic breast cancer, but is also complicated by a 20% incidence of congestive heart failure (CHF). The purpose of this phase II trial was to evaluate the antineoplastic activity of the regimen in a multi-institutional setting and to reduce the incidence of cardiotoxicity by limiting treatment to a maximum of six cycles. PATIENTS AND METHODS: Fifty-two patients with advanced breast cancer received doxorubicin (60 mg/m2 by IV injection) followed 15 minutes later by paclitaxel (200 mg/m2 by IV infusion over 3 hours) every 3 weeks for four to six cycles. RESULTS: Objective responses occurred in 25 of 48 assessable patients (52%; 95% confidence interval [CI], 38% to 66%), including four complete responses (8%; 95% CI, 0% to 16%). The median cumulative doxorubicin dose given was 240 mg/m2 (range, 132 to 360 mg/m2). Eleven patients (21%) were documented as having a decrease in the LVEF below normal, including three patients (6%; 95% CI, 0% to 12%) who developed CHF. CONCLUSION: The doxorubicin/paclitaxel regimen that we used is unlikely to produce an objective response rate of more than 70% and a complete response rate of more than 20% in patients with metastatic breast cancer, and proved to be excessively cardiotoxic for use in the adjuvant setting.

Phase III Study of Intravenous Vinorelbine in Combination With Epirubicin Versus Epirubicin Alone in Patients With Advanced Breast Cancer: A Scandinavian Breast Group Trial (SBG9403)

2004 ◽  
Vol 22 (12) ◽  
pp. 2313-2320 ◽  
Author(s):  
Bent Ejlertsen ◽  
Henning T. Mouridsen ◽  
Sven T. Langkjer ◽  
Jorn Andersen ◽  
Johanna Sjöström ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Response Rate ◽  
Complete Response Rate ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Complete Response ◽  
Phase Iii ◽  
Severe Toxicity ◽  
Free Survival

Purpose To determine whether the addition of intravenous (IV) vinorelbine to epirubicin increased the progression-free survival in first-line treatment of metastatic breast cancer. Patients and Methods A total of 387 patients were randomly assigned to receive IV epirubicin 90 mg/m2 on day 1 and vinorelbine 25 mg/m2 on days 1 and 8, or epirubicin 90 mg/m2 IV on day 1. Both regimens were given every 3 weeks for a maximum of 1 year but discontinued prematurely in the event of progressive disease or severe toxicity. In addition, epirubicin was discontinued at a cumulative dose of 1,000 mg/m2 (950 mg/m2 from June 1999). Prior anthracycline-based adjuvant chemotherapy and prior chemotherapy for metastatic breast cancer was not allowed. Reported results were all based on intent-to-treat analyses. Results Overall response rates to vinorelbine and epirubicin, and epirubicin alone, were 50% and 42%, respectively (P = .15). The complete response rate was significantly superior in the combination arm (17% v 10%; P = .048) as was median duration of progression-free survival (10.1 months v 8.2 months; P = .019). Median survival was similar in the two arms (19.1 months v 18.0 months; P = .50). Leukopenia related complications, stomatitis, and peripheral neuropathy were more common in the combination arm. The incidences of cardiotoxicity and constipation were similar in both arms. Conclusion Addition of vinorelbine to epirubicin conferred a significant advantage in terms of complete response rate and progression-free survival, but not in terms of survival.

scholarly journals Randomized phase II study of single-agent epirubicin +/— verapamil in patients with advanced metastatic breast cancer

1993 ◽  
Vol 4 (1) ◽  
pp. 45-50 ◽  
Author(s):  
K. Mross ◽  
C. Bohn ◽  
L. Edler ◽  
W. Jonat ◽  
W. Queisser ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Single Agent ◽  
Metastatic Breast ◽  
Randomized Phase Ii

Safety and Efficacy of Using a Single Agent or a Phase II Agent Before Instituting Standard Combination Chemotherapy in Previously Untreated Metastatic Breast Cancer Patients: Report of a Randomized Study—Cancer and Leukemia Group B 8642

1999 ◽  
Vol 17 (5) ◽  
pp. 1397-1397 ◽  
Author(s):  
Mary E. Costanza ◽  
Raymond B. Weiss ◽  
I. Craig Henderson ◽  
Larry Norton ◽  
Donald A. Berry ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Phase Ii ◽  
Combination Chemotherapy ◽  
Single Agent ◽  
Metastatic Breast ◽  
Response Rates ◽  
Breast Cancer Patients ◽  
Safety And Efficacy

PURPOSE: We undertook a prospective, randomized phase III trial to evaluate the safety and efficacy of using a phase II agent before initiating therapy with standard combination chemotherapy in metastatic breast cancer patients. PATIENTS AND METHODS: A total of 365 women with measurable metastatic breast cancer, previously untreated with chemotherapy for their metastatic disease, were randomized to receive either immediate chemotherapy with cyclophosphamide, doxorubicin, and fluorouracil (CAF) or up to four cycles of one of five sequential cohorts of single-agent drugs: trimetrexate, melphalan, amonafide, carboplatin, or elsamitrucin, followed by CAF. RESULTS: The toxicity of each single agent followed by CAF was comparable to that of CAF alone. The cumulative response rates for the single agent followed by CAF were not statistically different from those of CAF alone (44% v 52%; P = .24). However, in the multivariate analysis, patients with visceral disease had a trend toward lower response rates on the phase II agent plus CAF arm (P = .078). Although survival and response duration also were not statistically significantly different between the two study arms (P = .074 and P = .069, respectively), there was a suggestion of benefit for the CAF-only arm. CONCLUSION: The brief use of a phase II agent, regardless of its efficacy, followed by CAF resulted in response rates, toxicities, durations of response, and survival statistically equivalent to those seen with the use of CAF alone. These findings support the use of a new paradigm for the evaluation of phase II agents in the treatment of patients with metastatic breast cancer.

Phase II study of goserelin for patients with postmenopausal metastatic breast cancer.

1993 ◽  
Vol 11 (8) ◽  
pp. 1529-1535 ◽  
Author(s):  
T Saphner ◽  
A B Troxel ◽  
D C Tormey ◽  
D Neuberg ◽  
N J Robert ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Response Rate ◽  
Single Agent ◽  
Metastatic Breast ◽  
Postmenopausal Breast Cancer ◽  
Complete Response ◽  
Serum Levels ◽  
Breast Cancer Patients ◽  
Before And After

PURPOSE To determine the response rate of postmenopausal breast cancer patients to the gonadotropin-releasing hormone (GN-RH) agonist, Zoladex (goserelin; ICI Pharma, Wilmington, DE). PATIENTS AND METHODS A multi-institutional single-agent trial in postmenopausal patients was conducted. Serum levels of follicle-stimulating hormone (FSH), testosterone, and estradiol were requested before and after Zoladex treatment. RESULTS For estrogen receptor-positive (ER+) patients, the response rate was 11%, with one complete response (CR) and three partial responses (PRs) among 36 eligible patients. Responses were of short duration. There were no responses among 16 estrogen receptor-negative (ER-) patients. CONCLUSION GN-RH agonists have activity in ER+ postmenopausal patients, but response rates are not as high as with other available endocrine therapies and the duration of response is short.

Phase III Trial of Doxorubicin, Paclitaxel, and the Combination of Doxorubicin and Paclitaxel as Front-Line Chemotherapy for Metastatic Breast Cancer: An Intergroup Trial (E1193)

2003 ◽  
Vol 21 (4) ◽  
pp. 588-592 ◽  
Author(s):  
George W. Sledge ◽  
Donna Neuberg ◽  
Patricia Bernardo ◽  
James N. Ingle ◽  
Silvana Martino ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Quality Of Life ◽  
Metastatic Breast Cancer ◽  
Single Agent ◽  
Metastatic Breast ◽  
Complete Response ◽  
Phase Iii ◽  
Global Quality Of Life ◽  
Intergroup Trial

Purpose: Between February 1993 and September 1995, 739 patients with metastatic breast cancer were entered on an Intergroup trial (E1193) comparing doxorubicin (60 mg/m2), paclitaxel (175 mg/m2/24 h), and the combination of doxorubicin and paclitaxel (AT, 50 mg/m2 and 150 mg/m2/24 h, plus granulocyte colony-stimulating factor 5 mg/kg) as first-line therapy. Patients receiving single-agent doxorubicin or paclitaxel were crossed over to the other agent at time of progression. Patients and Methods: Patients were well balanced for on-study characteristics. Results: Responses (complete response and partial response) were seen in 36% of doxorubicin, 34% of paclitaxel, and 47% of AT patients (P = .84 for doxorubicin v paclitaxel, P = .007 for v AT, P = .004 for paclitaxel v AT). Median time to treatment failure (TTF) is 5.8, 6.0, and 8.0 months for doxorubicin, paclitaxel, and AT, respectively (P = .68 for doxorubicin v paclitaxel, P = .003 for doxorubicin v AT, P = .009 for paclitaxel v AT). Median survivals are 18.9 months for patients taking doxorubicin, 22.2 months for patients taking paclitaxel, and 22.0 months for patients taking AT (P = not significant). Responses were seen in 20% of patients crossing from doxorubicin → paclitaxel and 22% of patients crossing from paclitaxel → doxorubicin (P = not significant). Changes in global quality-of-life measurements from on-study to week 16 were similar in all three groups. Conclusion: (1) doxorubicin and paclitaxel, in the doses used here, have equivalent activity; (2) the combination of AT results in superior overall response rates and time to TTF; and (3) despite these results, combination therapy with AT did not improve either survival or quality of life compared to sequential single-agent therapy.

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