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.

Activity of Exemestane in Metastatic Breast Cancer After Failure of Nonsteroidal Aromatase Inhibitors: A Phase II Trial

2000 ◽  
Vol 18 (11) ◽  
pp. 2234-2244 ◽  
Author(s):  
Per Eystein Lønning ◽  
Emilio Bajetta ◽  
Robin Murray ◽  
Michèle Tubiana-Hulin ◽  
Peter D. Eisenberg ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Partial Response ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Objective Response ◽  
Metastatic Breast ◽  
Complete Response ◽  
Attractive Alternative ◽  
Hormonal Therapies

PURPOSE: To evaluate the antitumor activity and toxicity of a new steroidal aromatase inactivator, exemestane, in postmenopausal women with metastatic breast cancer who had progressive disease (PD) after treatment with a nonsteroidal aromatase inhibitor. PATIENTS AND METHODS: In this phase II trial, eligible patients were treated with exemestane 25 mg daily (n = 241) followed, at the time PD was determined, by exemestane 100 mg daily (n = 58). RESULTS: On the basis of the intent-to-treat analysis by independent review, exemestane 25 mg produced objective responses in 6.6% of patients (95% confidence interval [CI], 3.8% to 10.6%) and overall success (complete response + partial response + no change for 24 weeks or longer) in 24.3% (95% CI, 19.0% to 30.2%). The median durations of objective response and overall success were 58.4 weeks (95% CI, 49.7 to 71.1 weeks) and 37.0 weeks (95% CI, 35.0 to 39.4 weeks), respectively. Increasing the dose of exemestane to 100 mg upon the development of PD produced one partial response (1.7%; 95% CI, 0.0% to 9.2%). Both dosages were well tolerated and were discontinued because of adverse events in only 1.7% of patients. CONCLUSION: Exemestane 25 mg once daily seems to be an attractive alternative to chemotherapy for the treatment of patients with metastatic breast cancer after multiple hormonal therapies have failed.

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.

Phase II Trial of Oral Tegafur and Folinic Acid with Mitoxantrone as First-Line Regimen in Patients with Metastatic Breast Cancer

1996 ◽  
Vol 82 (1) ◽  
pp. 61-64 ◽  
Author(s):  
Vicente Alonso ◽  
Carmen Santander ◽  
Jesús Florián ◽  
Martina Alonso ◽  
Ma Dolores Isla ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Folinic Acid ◽  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Metastatic Breast ◽  
Biochemical Modulation ◽  
Outpatient Basis ◽  
First Line

Background Tegafur acts as a deport form of 5-fluorouracil when administered orally for longs periods of time, since it is an active drug in metastatic breast cancer, with response rates of 29-44%. Biochemical modulation with folinic acid and the addition of mitoxantrone could increase the efficacy of tegafur in patients with metastatic breast cancer. Methods A prospective phase II trial in patients with previously untreated metastatic breast cancer was carried out. The scheme consisted of mitoxantrone, 12 mg/m2 intravenous day 1, oral tegafur, 750 mg/m2/day divided in three equal doses, and leucovorin 15 mg/8 h orally for days 1-21, given in a 4-week schedule. None patient had received chemotherapy for metastatic breast cancer, although 16 patients had received previous adjuvant chemotherapy. Results Thirty-four patients were included. Objective responses were achieved in 20 of 32 patients assessable for response, with 1 complete response and 19 partial responses. The objective response rate was 62.5% (95% confidence intervals, 48-76%). The median duration of response was 10 months. Grade III-IV toxicity according to WHO criteria was digestive (nausea/vomiting) in 12.5%, diarrhea in 25% and stomatitis in 25% of patients. Other toxicities were low. Eight patients required dose-reduction. Conclusions We achieved a significant response rate with the scheme, which was administered on an outpatient basis. It seems to be safe and effective as first-line treatment in metastatic breast cancer, with a short median response duration. The size of the trial does not permit definitive conclusions, and the role of biochemical modulation of tegafur in combination with mitoxantrone remains to be defined.

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.

Gemcitabine and Vinorelbine Combination Chemotherapy in Taxane-Pretreated Patients with Metastatic Breast Cancer: A Phase II Study of the Kinki Multidisciplinary Breast Oncology Group (KMBOG) 1015

Chemotherapy ◽  
2017 ◽  
Vol 62 (5) ◽  
pp. 307-313 ◽  
Author(s):  
Jun Yamamura ◽  
Norikazu Masuda ◽  
Daigo Yamamoto ◽  
Shigeru Tsuyuki ◽  
Masahide Yamaguchi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Study ◽  
Objective Response ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Breast Cancer Patients ◽  
Free Survival

Background: This phase II study was conducted to evaluate the efficacy and safety of the chemotherapy combination of gemcitabine and vinorelbine in taxane-pretreated Japanese metastatic breast cancer patients. Methods: In this multicenter, phase II, single-arm study, patients with recurrent or metastatic HER2-negative breast cancer were administered gemcitabine (1,200 mg/m2) and vinorelbine (25 mg/m2) intravenously on days 1 and 8 every 3 weeks. The primary endpoint was the objective response rate, and other endpoints included progression-free survival, overall survival, and safety. Results: A total of 42 patients were enrolled in this study. The objective response rate and clinical benefit rate were 24 and 43%, respectively. The median progression-free survival was 4.0 months. The median overall survival was 11.1 months. Grade 3/4 neutropenia was the most common hematologic toxicity, occurring in 22 patients (54%). Nonhematologic toxicity was moderate and transient, with fatigue (48%) being the most common condition and no severe adverse event reported. Conclusion: The combination of gemcitabine and vinorelbine is an effective and tolerable regimen for HER2-negative, taxane-pretreated, metastatic breast cancer patients in Japan.

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.

A phase II study of gemcitabine and liposomal doxorubicin (Lipo-Dox) as first line chemotherapy in the treatment of metastatic breast cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10688-10688
Author(s):  
N. Yao ◽  
W. Kao ◽  
T. Chao ◽  
R. Hsieh ◽  
J. Lin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Phase Ii ◽  
Stable Disease ◽  
Liposomal Doxorubicin ◽  
Overall Response Rate ◽  
Response Rate ◽  
Objective Response ◽  
Metastatic Breast ◽  
Overall Response

10688 Background: To determine the overall objective response rate (ORR) of Lipo-Dox plus Gemcitabine in patients with metastatic breast cancer. Patients and Methods: We are conducting an open-label, non-comparative phase II clinical trial in Simon’s 2-stage optimal design to assess the efficacy and the safety of the treatment with Gemcitabine (Gems) plus Liposomal Doxorubicin (Lipo-Dox) in patients with metastatic breast cancer. All eligible subjects received Lipo-Dox 25 mg/m2 intravenous infusion over 1 hr and follow by gemcitabine 800 mg/m2 intravenously (iv) over 30 minutes on day 1, and receive gemcitabine 800 mg/m2 intravenously (iv) over 30 minutes only on day 8 in a 21-day cycle. Results: Between July 2004 and December 2005, a total of 21 patients were enrolled in the study and total of 136 cycles of chemotherapy were delivered with a median of six per patients (range 1–16). 17 patients (80.8%) who had at least one post-treatment evaluation and exposed to at least two cycles of treatment were included in this report. Characteristics of the 17 patients: All females; median age 52 years (range 36 - 68); 16 pts had a performance status (PS) of 0 or 1 and 1 had a PS of 2 (ECOG scale); Histology: All metastatic breast cancer. The response assessment of the 17 patients: Complete response was observed in 2, partial response in 5, stable disease in 8, and progressive disease in 2 patients. Overall response rate was 41.17%. Major grade 3/4 hematological toxicities were neutropenia in 9 pts, thrombocytopenia in 2 pt and leukopenia in 5 pts. Peripheral neuropathy was noted in 1 patient (grade 2). Other toxicities occurred during the treatment cycles were all manageable or tolerable. Patient recruitment, treatment and follow-up are still ongoing. Conclusion: Liposomal Doxorubicin used in the regimen reduces the incidence of alopecia (hair loss) to grade 1 compare to the conventional doxorubicin. This study, with an overall response rate of 41.1% (CR+PR) and a rate of stable disease of 47.05%, has shown a good activity with mild and acceptable toxicities of Gemcitabine (Gems) plus Liposomal Doxorubicin (Lipo-Dox) regimen in patients with metastatic breast cancer. No significant financial relationships to disclose.

Phase II trial of docetaxel: a new, highly effective antineoplastic agent in the management of patients with anthracycline-resistant metastatic breast cancer.

1995 ◽  
Vol 13 (12) ◽  
pp. 2886-2894 ◽  
Author(s):  
V Valero ◽  
F A Holmes ◽  
R S Walters ◽  
R L Theriault ◽  
L Esparza ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Objective Response ◽  
Antineoplastic Agent ◽  
Metastatic Breast ◽  
Skin Toxicity ◽  
Fluid Retention ◽  
Survival Duration

PURPOSE To determine the efficacy (objective response rate and duration of response and survival) and toxicity of docetaxel in patients with strictly defined anthracycline-resistant metastatic breast cancer (MBC). PATIENTS AND METHODS Thirty-five patients with bidimensionally measurable MBC who had progressive disease while receiving anthracycline-containing chemotherapy were registered onto the phase II trial. Docetaxel was administered at a dose of 100 mg/m2 over 1 hour every 21 days. RESULTS Thirty-four patients were assessable for disease response; 18 (53%; 95% confidence interval [CI], 35% to 70%) achieved a partial response. The median times to disease progression and survival duration were 7.5 and 13.5 months, respectively, for responding patients. The median overall survival duration was 9 months. Two hundred eight cycles (median, five) of docetaxel were administered. Neutropenia with less than 500 cells/microL developed in 31 of 35 patients; it was complicated by fever in 30 (14%) of 208 cycles and in 18 (51%) of 35 patients, including one treatment-related death. Fluid retention was seen in 15 (43%) of 35 patients, including pleural effusions in 11 patients (31%). Moderate skin toxicity, asthenia, and myalgia were observed in 16%, 58%, and 37% of cycles, respectively. CONCLUSION Docetaxel has the highest reported antitumor activity in anthracycline-resistant MBC. High objective response rates were seen in patients with visceral-dominant involvement, multiple metastatic sites, or extensive previous therapy. Docetaxel is associated with severe but reversible neutropenia, asthenia, and cumulative dose-related fluid retention. Dexamethasone decreased the frequency and severity of skin toxicity and appeared to ameliorate fluid retention.

Phase II Trial of Anastrozole Plus Goserelin in the Treatment of Hormone Receptor–Positive, Metastatic Carcinoma of the Breast in Premenopausal Women

2010 ◽  
Vol 28 (25) ◽  
pp. 3917-3921 ◽  
Author(s):  
Robert. W. Carlson ◽  
Richard Theriault ◽  
Christine M. Schurman ◽  
Edgardo Rivera ◽  
Cathie T. Chung ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Antitumor Activity ◽  
Phase Ii ◽  
Hormone Receptor ◽  
Phase Ii Trial ◽  
Hot Flashes ◽  
Metastatic Breast ◽  
Premenopausal Women ◽  
Hormone Receptor Positive

Purpose To explore the antitumor activity of the aromatase inhibitor, anastrozole, in the treatment of premenopausal women with hormone receptor–positive, metastatic breast cancer who have been rendered functionally postmenopausal with the use of the luteinizing hormone-releasing hormone agonist, goserelin. Patients and Methods Premenopausal women with estrogen and/or progesterone receptor–positive, metastatic or recurrent breast cancer were enrolled in this prospective, single-arm, multicenter phase II trial. Patients were treated with goserelin 3.6 mg subcutaneous monthly and began anastrozole 1-mg daily 21 days after the first injection of goserelin. Patients continued on treatment until disease progression or unacceptable toxicity. Results Thirty-five patients were enrolled of which 32 were evaluable for response and toxicity. Estradiol suppression was assessed, with mean estradiol levels of 18.7 pg/mL at 3 months and 14.8 pg/mL at 6 months. One participant (3.1%) experienced a complete response, 11 (34.4%) experienced partial response, and 11 (34.4%) experienced stable disease for 6 months or longer for a clinical benefit rate of 71.9%. Median time to progression was 8.3 months (range, 2.1 to 63+) and median survival was not been reached (range, 11.1 to 63+). The most common adverse events were fatigue (50%), arthralgias (53%), and hot flashes (59%). There were no grade 4 to 5 toxicities. Conclusion The combination of goserelin plus anastrozole has substantial antitumor activity in the treatment of premenopausal women with hormone receptor–positive metastatic breast cancer.

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