Phase II Trial of Doxorubicin and Docetaxel Plus Granulocyte Colony-Stimulating Factor in Metastatic Breast Cancer: Eastern Cooperative Oncology Group Study E1196

2000 ◽  
Vol 18 (12) ◽  
pp. 2369-2377 ◽  
Author(s):  
Joseph A. Sparano ◽  
Anne O’Neill ◽  
Paul L. Schaefer ◽  
Carla I. Falkson ◽  
William C. Wood
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Metastatic Breast ◽  
Phase Iii ◽  
Left Ventricular Ejection ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Stimulating Factor

PURPOSE: The purpose of this multi-institutional phase II trial was to evaluate the efficacy and toxicity of doxorubicin and docetaxel plus granulocyte colony-stimulating factor (G-CSF) in patients with metastatic breast cancer. The primary objective was to determine whether the combination produced a response rate of at least 50%. PATIENTS AND METHODS: Fifty-four patients with metastatic breast cancer received doxorubicin (60 mg/m2 by intravenous [IV] injection) followed 1 hour later by docetaxel (60 mg/m2 by IV infusion over 1 hour) every 3 weeks for up to eight cycles. All patients also received G-CSF. RESULTS: Objective response occurred in 29 (57%) of 51 eligible patients (95% confidence interval [CI], 42% to 70%), including three patients who had a complete response (6%; 95% CI, 1% to 16%). The median response duration was 7 months (95% CI, 6.0 to 15.0 months), median time to treatment failure was 7.6 months (95% CI, 6.2 to 9.9 months), and the median survival was 27.5 months (95% CI, 21.5 months to upper limit not reached). The median cumulative doxorubicin dose was 395 mg/m2 (range, 60 to 480 mg/m2). Fifteen patients (28%) were documented to have a decrease in the left ventricular ejection fraction below normal, and three patients (6%; 95% CI, 1% to 15%) developed congestive heart failure. CONCLUSION: Using criteria that we had defined a priori, the doxorubicin-docetaxel regimen as used in this study was sufficiently active and tolerable to justify a phase III comparison with doxorubicin-cyclophosphamide in early-stage breast cancer.

Phase II trial of paclitaxel and topotecan with granulocyte colony-stimulating factor support in stage IV breast cancer.

1998 ◽  
Vol 16 (6) ◽  
pp. 2032-2037 ◽  
Author(s):  
G F Fleming ◽  
J W Kugler ◽  
P C Hoffman ◽  
R Ansari ◽  
J D Bitran ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Single Agent ◽  
Metastatic Breast ◽  
Pharmacokinetic Parameters ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Stage Iv Breast Cancer ◽  
Stimulating Factor

PURPOSE This multicenter phase II trial investigated the efficacy and safety of a combination of paclitaxel and topotecan in patients with pretreated metastatic breast cancer. Plasma levels of paclitaxel and topotecan were obtained during cycle 1 to correlate pharmacokinetic parameters with toxicity. PATIENTS AND METHODS Paclitaxel was administered intravenously (i.v.) at 230 mg/m2 over 3 hours on day 1 followed by topotecan 1.0 mg/m2 i.v. over 30 minutes on days 1 to 5. Patients received an abbreviated premedication regimen that consisted of ranitidine 50 mg, diphenhydramine 50 mg, and a single 20-mg dose of dexamethasone, all administered i.v. 30 minutes before paclitaxel. Granulocyte colony-stimulating factor (GCSF) was administered at 5 micrograms/kg/d subcutaneously starting on day 6 and continuing until the absolute granulocyte count (AGC) was greater than 10,000/microL. Plasma paclitaxel and topotecan concentrations were assessed during the first cycle using limited-sampling strategies. RESULTS Seventeen patients were treated. The majority had visceral metastases. Four patients experienced neutropenic fever and one had mild bronchospasm. Only one partial response (PR) was observed. Nadir AGC correlated strongly with both duration of paclitaxel levels greater than 0.05 mumol/L and maximum concentration (Cmax) of paclitaxel. CONCLUSION This regimen does not produce a response rate superior to that expected with single-agent paclitaxel at doses that do not require growth factor support.

Phase I/II study of 72-hour infusional paclitaxel and doxorubicin with granulocyte colony-stimulating factor in patients with metastatic breast cancer.

1996 ◽  
Vol 14 (3) ◽  
pp. 774-782 ◽  
Author(s):  
J S Fisherman ◽  
K H Cowan ◽  
M Noone ◽  
A Denicoff ◽  
S Berg ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Phase I ◽  
Overall Response Rate ◽  
Response Rate ◽  
Metastatic Breast ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Stimulating Factor ◽  
Doxorubicin Administration

PURPOSE We conducted a phase I/II trial of concurrently administered 72-hour infusional paclitaxel and doxorubicin in combination with granulocyte colony-stimulating factor (G-CSF) in patients with previously untreated metastatic breast cancer and bidimensionally measurable disease. PATIENTS AND METHODS We defined the maximum-tolerated dose (MTD) of concurrent paclitaxel and doxorubicin administration and then studied potential pharmacokinetic interactions between the two drugs. Forty-two patients who had not received prior chemotherapy for metastatic breast cancer received 296 total cycles of paclitaxel and doxorubicin with G-CSF. RESULTS The MTD was determined to be paclitaxel 180 mg/m2 and doxorubicin 60 mg/m2 each by 72-hour infusion with G-CSF. Diarrhea was the dose-limiting toxicity (DLT) of this combination, with three of three patients developing abdominal computed tomographic (CT) scan evidence of typhlitis (cecal thickening) at the dose level above the MTD. All patients developed grade 4 neutropenia (absolute neutrophil count [ANC] < 500 microL), generally less than 5 days in duration. This combination was generally safely administered at dose levels at or below the MTD. The overall response rate was 72% (28 of 39 patients; 95% confidence interval [CI], 55% to 85%), with 8% complete responses (CRs) (three of 39; 95% CI, 2% to 21%) and a median response duration of 9 months. The median overall survival time for all patients is 23 months, with a median follow-up duration of 28 months. Pharmacokinetic studies showed that administration of paclitaxel and doxorubicin together by 72-hour infusion did not affect the steady-state concentrations of either drug. CONCLUSION Concurrent 72-hour infusional paclitaxel and doxorubicin can be administered safely, but is associated with significant toxicity. The overall response rate of this combination in untreated metastatic breast cancer patients is similar to that achieved with other doxorubicin-based combination regimens. The modest complete response rate achieved suggests that this schedule of paclitaxel and doxorubicin administration does not produce significant additive or synergistic cytotoxicity against breast cancer.

Phase I study of paclitaxel in combination with cyclophosphamide and granulocyte colony-stimulating factor in metastatic breast cancer patients.

1996 ◽  
Vol 14 (1) ◽  
pp. 95-102 ◽  
Author(s):  
A W Tolcher ◽  
K H Cowan ◽  
M H Noone ◽  
A M Denicoff ◽  
D R Kohler ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Phase I ◽  
Phase I Study ◽  
Metastatic Breast ◽  
Ambulatory Setting ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Breast Cancer Patients ◽  
Stimulating Factor

PURPOSE In vitro data suggest that prolonged exposure to paclitaxel enhances breast cancer cytotoxicity. Our objective in this phase I study was to determine the tolerability of paclitaxel administered by 72-hour continuous intravenous (i.v.) infusion (CIVI) in combination with high-dose cyclophosphamide and granulocyte colony-stimulating factor (G-CSF) in the ambulatory setting to metastatic breast cancer patients. PATIENTS AND METHODS Paclitaxel was administered over 72 hours by CIVI and cyclophosphamide was given daily by i.v. bolus on days 1, 2, and 3, followed by G-CSF every 21 days. The availability of ambulatory infusion pumps and paclitaxel-compatible tubing permitted outpatient administration. RESULTS Fifty-five patients with metastatic breast cancer who had been previously treated with a median of two prior chemotherapy regimens were entered onto the study. Dose-limiting toxicity of grade 4 neutropenia for longer than 5 days and grade 4 thrombocytopenia occurred in three of five patients treated with paclitaxel 160 mg/m2 CIVI and cyclophosphamide 3,300 mg/m2 followed by G-CSF. The maximum-tolerated dose (MTD) was paclitaxel 160 mg/m2 CIVI and cyclophosphamide 2,700 mg/m2 in divided doses with G-CSF. Nonhematologic toxicities were moderate and included diarrhea, mucositis, and arthalgias. Although hemorrhagic cystitis developed in six patients, recurrence was prevented with i.v. and oral mesna, which permitted continued outpatient delivery. One hundred seventy-four cycles were safely administered in the ambulatory setting using infusional pumps and tubing. Objective responses occurred in 23 (one complete and 22 partial) of 42 patients with bidimensionally measurable disease (55%; 95% confidence interval, 38% to 70%), with a response rate of 73% (11 of 15) seen at the highest dose levels. CONCLUSION Paclitaxel by 72-hour CIVI with daily cyclophosphamide followed by G-CSF can be administered safely in the ambulatory setting, has acceptable toxicity, and is an active regimen in the treatment of metastatic breast cancer.

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.

Paclitaxel and recombinant human granulocyte colony-stimulating factor as initial chemotherapy for metastatic breast cancer.

1993 ◽  
Vol 11 (10) ◽  
pp. 1943-1951 ◽  
Author(s):  
B S Reichman ◽  
A D Seidman ◽  
J P Crown ◽  
R Heelan ◽  
T B Hakes ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Metastatic Disease ◽  
Objective Response ◽  
Metastatic Breast ◽  
Neutropenic Fever ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Highly Active ◽  
Stimulating Factor

PURPOSE A phase II study of Taxol (paclitaxel; Bristol-Myers Squibb Co, Princeton, NJ) as initial chemotherapy for metastatic breast cancer was conducted. Recombinant human granulocyte colony-stimulating factor (rhG-CSF) was used to ameliorate myelosuppression, the anticipated dose-limiting toxicity. PATIENTS AND METHODS Twenty-eight patients with bidimensionally measurable breast cancer who had not received prior chemotherapy for metastatic disease were treated. Taxol was administered at 250 mg/m2 as a continuous 24-hour intravenous (i.v.) infusion every 21 days. rhG-CSF was administered at 5 micrograms/kg/d subcutaneously on days 3 through 10. RESULTS Objective responses were observed in 16 of 26 assessable patients (62%; 95% confidence interval, 41% to 80%). There were three (12%) complete responses (CRs) and 13 (50%) partial responses (PRs). Ten of 16 patients (63%) who had received prior adjuvant chemotherapy responded, which included one CR and four PRs among eight patients who had received prior doxorubicin-containing therapy. Responses were observed in all sites of metastatic disease. The median time to first objective response was 5 weeks (range, 1 to 14). Administration of rhG-CSF was associated with a short duration of neutropenia (median, 2 days with absolute neutrophil count < 500 cells/microL). Eight of 26 patients (31%) who received more than one course received subsequent therapy without dose reduction. One hundred seventy-eight cycles of treatment were administered, with a median of six cycles per patient (range, one to 19). Eight courses (4.5%) were associated with admissions for neutropenic fever. Twenty-two patients (79%) did not require admission for neutropenic fever. Treatment was well tolerated. Adverse effects included generalized alopecia in all patients. Myalgias, arthralgias, and peripheral neuropathy were mild. No hypersensitivity reactions and no cardiac toxicity were observed. CONCLUSION Taxol is highly active as initial chemotherapy for metastatic breast cancer. Administration of rhG-CSF reduced the incidence, depth, and duration of neutropenia, compared with published prior experience. Further studies of Taxol in breast cancer, including combinations with other active agents, are clearly warranted.

North Central Cancer Treatment Group (NCCTG)

2006 ◽  
Vol 9 (S1) ◽  
pp. 340-372
Author(s):  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Phase Ii Study ◽  
Metastatic Breast ◽  
Phase Iii ◽  
First Line ◽  
North Central ◽  
Phase Iii Trial

This section provides current contact details and a summary of recent or ongoing clinical trials being coordinated by North Central Cancer Treatment Group (NCCTG). Clinical trials include: N9831: Phase III trial of doxorubicin and cyclophosphamide (AC) followed by weekly paclitaxel with or without trastuzumab as adjuvant treatment for women with HER2 over-expressing or amplified node positive or high-risk node negative breast cancer.N063D, BIG 2–06: Phase III Trial of Trastuzumab and/or Lapatinib in Patients with HER2+ Breast CancerN0537: Phase II Trial of VEGF Trap in Patients with Metastatic Breast Cancer Previously Treated with Anthracycline and/or TaxaneN0531: Phase II trial of weekly NAB (nanoparticle albumin bound)-paclitaxel (nab-paclitaxel) (abraxane) in combination with gemcitabine in patients with metastatic breast cancer.N0437: Phase II trial of CT-2103 (Xyotax) with capecitabine as first-line chemotherapy for patients with metastatic breast cancer.N0436: Phase II trial of concurrent irinotecan plus cetuximab in patients with advanced breast cancer with prior anthracycline and/or taxane-containing therapy.N0434: The Association of Breast Density Changes, Plasma Hormone Changes, and Breast Cancer Recurrence: a companion study to NCIC CTG MA 27N0432: Phase II trial of docetaxel with capecitabine and bevacizumab as first-line chemotherapy for patients with metastatic breast cancer.N0338: Phase II trial of docetaxel and carboplatin administered every 2 weeks as induction therapy for stage II or III breast cancer.N0337: Phase II study of capecitabine in combination with vinorelbine and trastuzumab for the first- or second-line treatment of HER2 metastatic breast cancer.N0336: Phase II trial of RAF kinase inhibitor BAY 43-9006 as single oral agent in patients with metastatic breast cancer previously exposed to anthracycline and/or taxane.N0332: Phase II trial of weekly irinotecan and docetaxel in refractory metastatic breast cancer.N0234: Phase II study of OSI-774 (Tarceva) and gemcitabine for patients with metastatic breast cancer.N0032: Phase II trial of Faslodex in women with metastatic breast cancer and failure on aromatase inhibitor therapy.N0031: A phase II study of topical ceramide lipids as treatment for cutaneous breast cancer.

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