Randomized Phase II Study of Two Irinotecan Schedules for Patients With Metastatic Breast Cancer Refractory to an Anthracycline, a Taxane, or Both

2004 ◽  
Vol 22 (14) ◽  
pp. 2849-2855 ◽  
Author(s):  
Edith A. Perez ◽  
David W. Hillman ◽  
James A. Mailliard ◽  
James N. Ingle ◽  
J. Michael Ryan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Metastatic Breast Cancer ◽  
Phase Ii ◽  
Median Overall Survival ◽  
Phase Ii Study ◽  
Objective Response ◽  
Metastatic Breast ◽  
Response Duration ◽  
Median Response

Purpose A pressing need exists for agents active against anthracycline- or taxane-refractory metastatic breast cancer (MBC), or both. Previous clinical trials suggested that irinotecan might have such activity. We conducted this multicenter phase II study to assess efficacy and tolerability of two irinotecan schedules. Patients and Methods MBC patients who experienced disease progression after one to three chemotherapy regimens, including at least one anthracycline- or taxane-based regimen, were randomly assigned to irinotecan in 6-week cycles comprising 100 mg/m2 weekly for 4 weeks, then a 2-week rest (weekly) or 240 mg/m2 every 3 weeks. Results The weekly arm had 52 assessable patients; the every-3-weeks arm had 51 assessable patients. In the weekly arm, the objective response (complete regression [CR] + partial regression [PR]) rate was 23% (one CR, 11 PR; 95% CI, 13% to 37%). Median response duration was 4.9 months (range, 1.9 to 15.9 months), and median overall survival was 9.7 months (95% CI, 8.0 to 14.2 months). In the every-3-weeks arm, the objective response rate was 14% (nine PR; 95% CI, 6% to 26%), median response duration was 4.2 months (range, 3.1 to 13.9 months), and median overall survival was 8.6 months (95% CI, 7.0 to 12.3 months). Treatment generally was well tolerated, especially in the weekly arm. Grade 3 to 4 adverse events with ≥ 10% incidence included neutropenia (29%) and diarrhea (17%) in the weekly arm and neutropenia (36%), vomiting (20%), dyspnea (18%), nausea (16%), and diarrhea (12%) in the every-3-weeks arm. Conclusion Irinotecan is active with good tolerability in refractory MBC. Irinotecan (especially weekly) warrants additional study as monotherapy and in combination regimens in this setting.

Ninety-six-hour paclitaxel infusion after progression during short taxane exposure: a phase II pharmacokinetic and pharmacodynamic study in metastatic breast cancer.

1996 ◽  
Vol 14 (6) ◽  
pp. 1877-1884 ◽  
Author(s):  
A D Seidman ◽  
D Hochhauser ◽  
M Gollub ◽  
B Edelman ◽  
T J Yao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Phase Ii ◽  
Drug Exposure ◽  
Metastatic Breast ◽  
Response Duration ◽  
Pharmacokinetic Profile ◽  
Primary Resistance ◽  
Secondary Resistance ◽  
Median Response

PURPOSE A phase II trial of paclitaxel infused over 96 hours in patients with metastatic breast cancer with demonstrated disease progression (PD) during short-infusion taxane treatment was performed to evaluate schedule-dependent activity with prolonged drug exposure. The tolerability of this strategy and its pharmacokinetic profile and pharmacodynamic correlates were also investigated. PATIENTS AND METHODS Paclitaxel was administered to 26 patients with metastatic breast cancer at 120 to 140 mg/m2 intravenously over 96 hours. Twenty-three patients had demonstrated PD while receiving prior 3-hour paclitaxel, two during 1-hour docetaxel, and one during infusions of docetaxel and then paclitaxel. Twenty-one patients (81%) had no prior response to the short taxane infusion (primary resistance) and five (19%) had prior partial responses (PRs) of brief duration before PD (secondary resistance). Plasma paclitaxel concentrations were assessed at 24, 48, 72, and 96 hours. RESULTS After delivery of 195 cycles, seven of 26 assessable patients (26.9%; 95% confidence interval, 11.6% to 47.8%) had major objective responses, with a median response duration of 6 months (range, 1 to 13). The predominant toxicities were neutropenia (76% grade > or = 3) and stomatitis (15% grade > or = 3). Despite omission of premedications, no significant hypersensitivity reactions occurred. The median steady-state paclitaxel concentration (Css) in 23 assessable patients was 0.047 mumol/L (range, .023 to .176). Patients who experienced grade 4 neutropenia had significantly decreased paclitaxel clearance and higher Css than those with grade 1 to 3 neutropenia (P < .05). Pretreatment elevation of hepatic transaminases was associated with delayed clearance (P < .01) and increased myelo-suppression and mucosal toxicity. CONCLUSION Paclitaxel demonstrates activity against metastatic breast cancer when administered over 96 hours to patients with disease that recently had progressed during short taxane exposure. Delayed paclitaxel clearance and consequent increased toxicity occurred in patients with hepatic dysfunction. The activity observed supports preclinical data that suggest variability in efficacy and resistance patterns to paclitaxel based on duration of exposure.

Phase II trial of docetaxel in advanced anthracycline-resistant or anthracenedione-resistant breast cancer.

1995 ◽  
Vol 13 (12) ◽  
pp. 2879-2885 ◽  
Author(s):  
P M Ravdin ◽  
H A Burris ◽  
G Cook ◽  
P Eisenberg ◽  
M Kane ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Response Rate ◽  
Objective Response ◽  
Metastatic Breast ◽  
Response Duration ◽  
Fluid Retention ◽  
Skin Reactions ◽  
Median Response ◽  
High Level

PURPOSE The purpose of this study was to evaluate the clinical efficacy and safety of docetaxel in patients with metastatic breast cancer (MBC) resistant to doxorubicin or mitoxantrone. PATIENTS AND METHODS Docetaxel 100 mg/m2 was administered as a 1-hour intravenous (IV) infusion every 3 weeks to 42 patients registered at four centers. Patients must have received at least one but no more than two prior chemotherapy regimens for MBC (in addition to any prior adjuvant therapy). One of the regimens for metastatic breast cancer must have included an anthracycline or anthracenedione and the cancer must have progressed on that regimen. RESULTS Objective responses were seen in 20 of 35 assessable patients (three complete responses [CRs] and 17 partial responses [PRs]), for an objective response rate of 57% (95% confidence interval [CI], 39% to 74%) and in 21 of 42 registered patients (50% response rate [RR]; 95% CI, 34% to 66%) entered onto the trial. The median response duration was 28 weeks. The most common toxicity in this study was grade 4 neutropenia, which occurred in 95% of patients. Other clinically significant nonhematologic side effects included stomatitis, skin reactions, neurosensory changes, asthenia, and fluid retention. Patients who received dexamethasone premedication had a later onset of fluid retention than those who did not receive dexamethasone (onset at a median cumulative docetaxel dose of 503 mg/m2 and 291 mg/m2, respectively). CONCLUSION Docetaxel at this dose and schedule has a high level of antitumor activity in patients with treatment-refractory advanced breast cancer, and appears to be one of the most active agents for the treatment of this patient population.

Randomized, Placebo-Controlled, Double-Blind, Phase II Study of Axitinib Plus Docetaxel Versus Docetaxel Plus Placebo in Patients With Metastatic Breast Cancer

2011 ◽  
Vol 29 (18) ◽  
pp. 2459-2465 ◽  
Author(s):  
Hope S. Rugo ◽  
Alison T. Stopeck ◽  
Anil A. Joy ◽  
Stephen Chan ◽  
Shailendra Verma ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Adjuvant Chemotherapy ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Objective Response ◽  
Metastatic Breast ◽  
Double Blind ◽  
The Difference ◽  
To Receive

Purpose This multicenter, randomized, double-blind, phase II study assessed safety and efficacy of axitinib plus docetaxel in metastatic breast cancer (MBC). Patients and Methods Women with MBC were randomly assigned 2:1 to receive docetaxel 80 mg/m2 once every 3 weeks plus axitinib 5 mg twice per day (combination arm) or placebo (placebo arm), following a lead-in phase I trial. The primary end point was time to progression (TTP). Results In all, 168 patients were enrolled; 112 were randomly assigned to axitinib and 56 to placebo. Median TTP was numerically longer in the combination arm than in the placebo arm (8.1 v 7.1 months), but this difference was not statistically significant (hazard ratio, 1.24; 95% CI, 0.82 to 1.87; one-sided P = .156). The difference in median TTP was greatest among patients who had received prior adjuvant chemotherapy (9.2 v 7.0 months; P = .043, prespecified subgroup analysis). Objective response rate was higher in the combination arm (41.1% v 23.6%; P = .011). The most common grades 3 to 4 treatment-related adverse events (combination/placebo) included diarrhea (10.8%/0%), fatigue (10.8%/5.4%), stomatitis (12.6%/1.8%), mucositis (9.0%/0%), asthenia (7.2%/0%), and hypertension (4.5%/0%). Three patients in the combination arm experienced serious thromboembolic events (one death). Febrile neutropenia was more frequent in the combination arm (15.3% v 7.1%); rates of other hematologic toxicities were comparable. Increased toxicity with axitinib was generally managed by dose reduction and/or growth factor support. Conclusion The addition of axitinib to docetaxel did not improve TTP in first-line MBC treatment. Combination therapy may be more effective in patients previously exposed to adjuvant chemotherapy.

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.

Phase II study of receptor-enhanced chemosensitivity using recombinant humanized anti-p185HER2/neu monoclonal antibody plus cisplatin in patients with HER2/neu-overexpressing metastatic breast cancer refractory to chemotherapy treatment.

1998 ◽  
Vol 16 (8) ◽  
pp. 2659-2671 ◽  
Author(s):  
M D Pegram ◽  
A Lipton ◽  
D F Hayes ◽  
B L Weber ◽  
J M Baselga ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Monoclonal Antibody ◽  
Metastatic Breast Cancer ◽  
Disease Progression ◽  
Phase Ii ◽  
Metastatic Breast ◽  
Response Duration ◽  
Pharmacokinetic Parameters ◽  
Minor Response ◽  
Median Response

PURPOSE To determine the toxicity, pharmacokinetics, response rate, and response duration of intravenous (i.v.) administration of recombinant, humanized anti-p185HER2 monoclonal antibody (rhuMAb HER2) plus cisplatin (CDDP) in a phase II, open-label, multicenter clinical trial for patients with HER2/neu-overexpressing metastatic breast cancer. PATIENTS AND METHODS The study population consisted of extensively pretreated advanced breast cancer patients with HER2/neu overexpression and disease progression during standard chemotherapy. Patients received a loading dose of rhuMAb HER2 (250 mg i.v.) on day 0, followed by weekly doses of 100 mg i.v. for 9 weeks. Patients received CDDP (75 mg/m2) on days 1, 29, and 57. RESULTS Of 37 patients assessable for response, nine (24.3%) achieved a PR, nine (24.3%) had a minor response or stable disease, and disease progression occurred in 19 (51.3%). The median response duration was 5.3 months (range, 1.6-18). Grade III or IV toxicity was observed in 22 of 39 patients (56%). The toxicity profile reflected that expected from CDDP alone with the most common toxicities being cytopenias (n = 10), nausea/vomiting (n = 9), and asthenia (n = 5). Mean pharmacokinetic parameters of rhuMAb HER2 were unaltered by coadministration of CDDP. CONCLUSION The use of rhuMAb HER2 in combination with CDDP in patients with HER2/neu-overexpressing metastatic breast cancer results in objective clinical response rates higher than those reported previously for CDDP alone, or rhuMAb HER2 alone. In addition, the combination results in no apparent increase in toxicity. Finally, the pharmacology of rhuMAb HER2 was unaffected by coadministration with CDDP.

Phase II Study of Pegylated Liposomal Doxorubicin in Combination With Gemcitabine in Patients With Metastatic Breast Cancer

2003 ◽  
Vol 21 (17) ◽  
pp. 3249-3254 ◽  
Author(s):  
Edgardo Rivera ◽  
Vicente Valero ◽  
Banu Arun ◽  
Melanie Royce ◽  
Rosni Adinin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Metastatic Breast Cancer ◽  
Phase Ii ◽  
Liposomal Doxorubicin ◽  
Metastatic Breast ◽  
Pegylated Liposomal Doxorubicin ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Median Response

Purpose: We conducted a phase II clinical trial to determine the clinical efficacy and safety of pegylated liposomal doxorubicin in combination with gemcitabine in patients with metastatic breast cancer. Patients and Methods: Patients were eligible if they had measurable disease, no prior chemotherapy for metastatic disease, and a performance status ≤ 2 on the Zubrod scale. Patients received pegylated liposomal doxorubicin 24 mg/m2 intravenously on day 1, plus gemcitabine 800 mg/m2 intravenously on days 1 and 8 of each 21-day cycle. Results: Of 49 patients enrolled, 27 had received prior adjuvant chemotherapy (19 with an anthracycline). Prior median cumulative anthracycline dose was 240 mg/m2. In total, three complete responses and 21 partial responses were achieved in 46 assessable patients, for an overall response rate of 52% (95% confidence interval, 37% to 67%). Responses were observed in 11 (58%) of 19 patients with previous anthracycline exposure. Median response duration was 5.6 months, time to progression was 4.5 months, and overall survival was 16.1 months. Although the most common grade 3 to 4 toxicities were hematologic, few neutropenic complications resulted. The most frequent nonhematologic toxicities were nausea and vomiting, fatigue, stomatitis, and hand-foot syndrome. One patient previously treated with an anthracycline developed a transient decrease (21%) in the left ventricular ejection fraction, with cardiac function recovering within 2 months. Conclusion: Pegylated liposomal doxorubicin in combination with gemcitabine is active and well tolerated in patients with metastatic breast cancer. Median overall survival was 16.1 months, and approximately 78% of patients derived clinical benefit from treatment. This regimen represents a therapeutic option for patients receiving front-line therapy for their metastatic breast cancer.

An open-label, phase II study of rucaparib, a PARP inhibitor, in HER2- metastatic breast cancer patients with high genomic loss of heterozygosity: RUBY.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS1117-TPS1117 ◽  
Author(s):  
Anne Patsouris ◽  
Cecile Vicier ◽  
Loic Campion ◽  
Wilfried Gouraud ◽  
Marta Jimenez ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Homologous Recombination ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Phase 1 ◽  
Objective Response ◽  
Snp Array ◽  
Metastatic Breast ◽  
Open Label

TPS1117 Background: BRCA1 and/or BRCA2 mutations confer sensitivity to poly(ADP-ribose) polymerase (PARP) inhibitors (PARPi). In addition to BRCA1/2, alterations of other genes (PALB2, RAD51C….) implicated in homologous recombination repair (HRR) pathways leads to a BRCAness phenotype that is also associated with PARPi sensitivity. Rucaparib, a potent oral PARP-1, -2 and -3 inhibitor, has shown activity in a phase 1 study of patients (pts) with homologous recombination deficient (HRD) breast cancer (Kristeleit, RS. J Clin Oncol 32:5s, 2014 [suppl; abstr 2573]). This single arm, open-label, multicenter phase II study (NCT02505048) is evaluating the efficacy and safety of rucaparib in pts with HER2- metastatic breast cancer (MBC) associated with a BRCAness phenotype determined by “high tumor genomic LOH” score and/or a somatic BRCAmutation. Methods: Pts with HER2- MBC exhibiting a BRCAness phenotype will receive oral rucaparib 600 mg BID continuously in 21-day cycles until disease progression. The primary endpoint is clinical benefit rate (CBR), defined by complete and partial response and stable disease lasting for at least 16 weeks and, if CBR is significant, the objective response rate (ORR). Secondary endpoints include progression-free survival, overall survival, safety, and the prognostic value of the BRCAness signature. Targeted enrollment is 41 pts using a Simon two-stage design. Eligibility: Women with HER2- MBC with a BRCAness phenotype who received 1-4 prior chemotherapy regimens are eligible. ECOG PS 0-1 and adequate organ function is required. The BRCAness phenotype is defined by high tumor genomic LOH (LOH cutoff of 18%) that can identify HRD tumors, including both known BRCA1 methylation and unknown genetic/epigenetic mechanisms and somatic BRCA1/2 mutations. Pts with a known BRCA1 and/or BRCA2 germline mutation are excluded. “high tumor genomic LOH” score will be generated from the CytoScan HD SNP array, which is available from the SAFIR02 protocol or other molecular programs. To date, 13 pts have been enrolled, with enrollment ongoing. This trial design is intended to establish proof-of-concept that rucaparib can improve ORR in HER2- MBC with HRD. Clinical trial information: NCT02505048.

Phase II Study of Docetaxel, Doxorubicin, and Cyclophosphamide as First-Line Chemotherapy for Metastatic Breast Cancer

2001 ◽  
Vol 19 (2) ◽  
pp. 314-321 ◽  
Author(s):  
J. M. Nabholtz ◽  
J. R. Mackey ◽  
M. Smylie ◽  
A. Paterson ◽  
D. R. Noël ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Objective Response ◽  
Metastatic Breast ◽  
Fluid Retention ◽  
First Line ◽  
Grade 3 ◽  
Line Chemotherapy

PURPOSE: This pilot phase II study investigated the efficacy and toxicity of docetaxel with doxorubicin and cyclophosphamide (TAC) as first-line chemotherapy for anthracycline-naive patients with metastatic breast cancer. PATIENTS AND METHODS: Fifty-four patients received a total of 359 courses consisting of docetaxel 75 mg/m2 given intravenously (IV) over 1 hour, preceded by IV doxorubicin 50 mg/m2 and cyclophosphamide 500 mg/m2 for a maximum of eight 3-week cycles. RESULTS: After an independent panel review, the overall objective response rate was 77% (complete response, 6%). Overall objective response rates in patients with visceral, bone, and liver involvement were 82%, 82%, and 80%, respectively. Median duration of response was 52 weeks, and median time to progression was 42 weeks. With a median follow-up of 32 months, the median survival had not yet been reached, whereas the 2-year survival was 57%. The main toxicities were hematologic (neutropenia grade 3/4 in 100% of patients and 95% of cycles; febrile neutropenia in 34% of patients and 9% of cycles). Documented grade 3 infection was seen in one patient (2%) in one cycle, and no toxic death was reported. Severe acute or chronic nonhematologic adverse events were infrequent, and docetaxel-specific toxicities (such as fluid retention and nail changes) were mild, with only one patient being discontinued for fluid retention. Congestive heart failure was seen in two patients (4%). CONCLUSION: TAC is an active and manageable regimen that has been chosen as the basis of five randomized phase III trials, including two pivotal studies comparing TAC to fluorouracil plus doxorubicin and cyclophosphamide in the metastatic and adjuvant treatment of breast cancer.

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