Gemcitabine plus carboplatin for patients with pretreated, metastatic breast cancer: A phase II trial

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10635-10635
Author(s):  
D. Laessig ◽  
U. Vehling-Kaiser ◽  
P. Fasching ◽  
F. Melchert ◽  
H. Koelbl ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Phase Ii ◽  
Remission Rate ◽  
Alkylating Agents ◽  
Metastatic Breast ◽  
Median Number ◽  
Primary Objective ◽  
Treatment Regimens ◽  
Present Trial

10635 Background: In search for treatment regimens which can be applied in anthracycline- and taxane-pretreated patients, the combination of gemcitabine and cisplatin was shown to be effective in several trials. To improve on tolerability and handling of the regimen, cisplatin was replaced by carboplatin in the present trial. Methods: Patients with intensively pretreated, metastatic breast cancer (age 18 to 70 years) and measurable disease were treated with gemcitabine (1000 mg/m2 iv on days 1 and 8) and carboplatin (AUC 4 iv on day 1) in a 3-week regimen. The trial was performed as a 2-stage phase II study according to the optimal design described by Simon (p0 = 0.1, p1 = 0.3, α = 0.05, β = 0.1) with overall remission rate (according to RECIST) as the the primary objective. Results: Of 39 recruited patients (median age: 60 years, range 29 to 77 years) response data are available from 35 patients. A positive hormone receptor status was observed in 77% of patients, and 31% of patients were Her-2 overexpressing. All patients had received prior chemotherapy, and 49% of patients had been subjected to 2 or more treatment regimens for metastastatic disease. Prior treatment consisted of anthracyclines (87%), alkylating agents (77%), taxanes (67%), and antimetabolites (62%). Prior endocrine therapy had been applied to 77% of patients. At the time of evaluation, a total of 183 treatment cycles were documented with a median number of 5 cycles per patient (range 1 to 11). Treatment is presently ongoing in 8 patients. A CR was observed in 1/35 patients, a PR in 8/35 patients for an overall remission rate of 26% (95%-CI: 12% to 43%). Stable disease was documented in 49% (17/35) of patients. Median time to progression was 4.9 months (95%-CI: 2.9 to 6.8 months). In 39 evaluable pts, CTC grade 3/4 leukopenia was observed in 22/2 pts, neutropenia in 14/8 pts, anemia in 3/0 pts, and thrombocytopenia in 11/8 pts. Treatment delays and/or dose reductions were performed in 49% of cycles. Conclusion: Gemcitabine in combination with carboplatin is an effective combination for second- or third-line treatment in patients with metastatic breast cancer. [Table: see text]

A randomized, open-label, phase II study of lapatinib / capecitabine, lapatinib / vinorelbine, or lapatinib / gemcitabine in patients with ErbB2-amplified metastatic breast cancer progressing after taxane treatment: Results of an interim analysis (GLICO-0801 / EGF111792).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e11087-e11087
Author(s):  
Henry Leonidas Gomez ◽  
Silvia P. Neciosup ◽  
Celia Tosello ◽  
Patricia Xavier ◽  
Yeni Neron do Nascimento ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Phase Ii ◽  
Interim Analysis ◽  
Metastatic Breast ◽  
Primary Objective ◽  
Open Label ◽  
Open Label Phase ◽  
Hand Foot Syndrome ◽  
Number Of Cycles

e11087 Background: Lapatinib-capecitabine is approved for the treatment of ErbB2-amplified metastatic breast cancer (MBC) after failure to anthracyclines, taxanes and trastuzumab. GLICO-0801 evaluates different lapatinib-based chemotherapy combinations as 1st/2nd line treatment for ErbB2 amplified MBC progressing after taxane treatment. We present the results of a planned safety interim analysis. Methods: This is an open-label, randomized, international, phase II trial exploring lapatinib (L) 1250mg qd in combination with capecitabine 2000mg/m2 d 1-14 (Arm A) or vinorelbine 25mg/m2 d 1 and 8 (Arm B) or gemcitabine 1000mg/m2 d 1 and 8 (Arm C). Primary objective is to determine the clinical benefit rate (defined as CR+PR+SD for ≥24 weeks). This trial is registered at www.clinicaltrials.gov number: NCT01050322 Results: The first83 randomized patients (pts) (Arm A=29, B=28 and C=26) were included in this analysis. Of them, 65 (78%) have discontinued therapy with mean number of cycles of 4.7, 6.2 and 7.5 in arms A, B and C respectively. Eighteen (21%) pts are still on treatment. Median age was 52y (29-84); 80 pts (96%) had PS 0-1; 51 (61%) were postmenopausal. Fifty-six pts (67%) had visceral metastasis, 52 (63%) were treated as 2nd line therapy and 36 (43%) had received prior trastuzumab. Most reported adverse events (AE) (87%) were grade 1-2. The most common AE (any grade) in arm A: diarrhea 72%, hand-foot syndrome 45%, vomiting 39%, anemia 36%; in arm B: diarrhea 75%, neutropenia 68%, nausea 43%, vomiting 39%; in arm C: diarrhea 72%, neutropenia 60%, anemia 44%, increase in ALT 44%. The most frequent serious AE reported in arm A: diarrhea in 3 pts (10%) and thrombocytopenia in 2 pts (7%); in arm B: febrile neutropenia in 2 pts (7%) and in arm C: sepsis in 1 pt (4%). There was one toxic death related to chemotherapy in arm C. Conclusions: There were no unexpected toxicities so far in this trial with most AEs being mild to moderate and manageable. This interim analysis supports the continuation of the study.

Phase II trial of RAD001 plus carboplatin in patients with triple-negative metastatic breast cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e11529-e11529
Author(s):  
Jasmeet Chadha Singh ◽  
Stacy Stein ◽  
Matthew Volm ◽  
Julia Anne Smith ◽  
Yelena Novik ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Phase Ii ◽  
Triple Negative Breast Cancer ◽  
Clinical Benefit ◽  
Triple Negative ◽  
Metastatic Breast ◽  
Primary Objective ◽  
Grade 3 ◽  
Platinum Agents

e11529 Background: Triple negative breast cancer cells are unable to repair double stranded DNA breaks and hence have sensitivity to platinum agents. Rapamycin acts synergistically with platinum agents to induce apoptosis and inhibit proliferation in breast cancer cell lines. Combination of RAD001 (oral mTOR inhibitor) and Carboplatin may have activity in triple-negative breast cancer. Methods: The primary objective of the study was to estimate the clinical benefit (complete remission (CR) + partial remission (PR) + stable disease (SD) >6 months) and the toxicity of this combination in women with triple negative metastatic breast cancer who have had 0-3 prior chemotherapy regimens for metastatic disease. 25 subjects were to be entered into a single stage open label Phase II study. Prior Carboplatin is allowed. Treated brain metastasis are eligible. The null hypothesis that the clinical benefit rate is ≤10% could be rejected if number of CR/PR/SD >6 months was ≥6. Originally, intravenous Carboplatin AUC 6 was to be administered every 3 weeks along with daily 5mg of RAD001 with a 3 patient run-in and then 10 mg daily. Due to a surprising amount of thrombocytopenia with this combination, the dose of Carboplatin was first amended to AUC 5 and most recently to AUC 4 with 5 mg of RAD001. Results: 18 patients have been recruited thus far. Median age is 59. There have been 1 CR, 4 PR’s and 2 SD's lasting > 6 months. One SD was achieved in a patient progressing on single agent Carboplatin at study entry. Median duration of CR+ SD +PR thus far is 13 weeks (range: 6-60 weeks). 5 patients had grade 3/4 thrombocytopenia and 4 patients had grade 3 neutropenia (no febrile neutropenia). However, since amendment of Carboplatin dose to AUC 4 the regimen has been well tolerated. 1 patient suffered from grade 3 dehydration. The estimated clinical benefit rate is 50% (95% C.I.: 24%, 76%). Median time to progression or death is 87.5 days from start of treatment; there is only 1 death to date on this study. Conclusions: The study has achieved it’s primary objective of demonstrating clinical benefit of RAD 001-Carboplatin combination in triple negative metastatic breast cancer. Dose limiting thrombocytopenia was an unexpected side effect requiring protocol amendment.

Phase II results of tasisulam-sodium in previously treated patients with metastatic breast cancer.

2012 ◽  
Vol 30 (27_suppl) ◽  
pp. 114-114 ◽  
Author(s):  
Lee Steven Schwartzberg ◽  
Hatem Hussein Soliman ◽  
Alison Katherine Conlin ◽  
Christopher O. Ruud ◽  
Haluk Tezcan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Phase Ii ◽  
Metastatic Breast ◽  
Primary Objective ◽  
Breast Cancer Cell Lines ◽  
Disease Rate ◽  
Lean Body Weight ◽  
Previously Treated Patients ◽  
Previously Treated

114 Background: Tasisulam, a novel acylsulfonamide antineoplastic agent, promotes apoptosis, exhibits antiangiogenic activities, and demontrates antiproliferative activity against human breast cancer cell lines. In humans, tasisulam is highly albumin bound, with a median half-life of approximately 11 days. Previous phase II studies of tasisulam indicated that an albumin-corrected exposure (AUCalb) range of 1200 to 6400 h*mcg/mL provided the optimal balance of efficacy and safety. This study investigates the drug’s activity in previously treated patients (pts) with metastatic breast cancer (mBC). Methods: Pts with at least 2 prior therapies for mBC andserum albumin level ≥3.0 g/dL received tasisulam by 2-hour infusion every 28 days, dosed by a lean body weight-based dosing algorithm targeting an AUCalb range of 1200 to 6400 h*mcg/mL. Primary objective was to show at least a 10% response rate (RR) using RECIST 1.0. Secondary objectives included progression-free survival (PFS), overall survival (OS), pharmacokinetics (PK), and safety. Results: Thirty-three pts received at least 1 dose of tasisulam. All were women, with a mean age of 55.4 (±9.7) years. Pts received a median of 2 cycles (ranges 1-8). The majority of pts achieved the target AUCalb range of 1200 to 6400 h*mcg/mL or higher in cycles 1 and 2 (63% and 69%, respectively). The most common tasisulam-related hematologic toxicities were grade 3 anemia (3.0%) and grade 4 neutropenia (6.1%). Common nonhematological adverse events possibly related to tasisulam were fatigue (39.4%), diarrhea (24.2%), and nausea (18.2%). No deaths were considered related to the study drug. The RR (1 CR, 1 PR) was 6.1% (90% CI: 1.1, 17.9), stable disease rate was 24% (n=8; 90% CI: 12.7, 39.5), with a median PFS of 1.81 months (90% CI: 1.64, 2.17) and a median OS of 6.77 months (90% CI: 4.37, 11.63). Conclusions: Tasisulam was reasonably well tolerated, but did not meet its primary objective of overall RR of 10% in this heavily pretreated mBC patient population. PK analysis of the albumin-tailored dosing regimen indicated that the majority of the patients achieved the target AUCalb or higher, suggesting that the modest activity observed was not due to suboptimal dosing.

Phase II study of vinorelbine and capecitabine as first-line treatment for metastatic breast cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e12004-e12004
Author(s):  
Wael El-Sadda ◽  
Inas Ibraheim Abdel Halim ◽  
Mohamed Abdel Aziz
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Phase Ii ◽  
Metastatic Breast ◽  
Complete Response ◽  
Median Number ◽  
Line Treatment ◽  
First Line ◽  
Number Of Cycles ◽  
First Line Treatment

e12004 Background: Vinorelbine (V) and capecitabine (C) are likely to have a synergisitic interaction. Vinorelbine upregulates thymidine phosphorylase; a key enzyme in the conversion of capecitabine to active 5-FU in tumor tissue. Available phase II clinical data reports response rates ranging from 48-70% in first line metastatic breast cancer (MBC) for this combination. We evaluated the efficacy and safety of vinorelbine plus capecitabine in patients with MBC relapsing after adjuvant anthracycline based treatment. Methods: Sixty patients were enrolled between Oct 2008 through Dec 2010. All patients had measurable MBC relapse after adjuvant anthracycline and/or taxanes, WHO PS < 2, adequate bone marrow, renal and hepatic functions. Patients received intravenous vinorelbine 25 mg/m2 on day 1 and 8 and oral capecitabine 1000 mg/m2 bid on days 1 to 14, cycles to be repeated every 3 weeks. Patients with PD went off the study while those with CR, PR or SD continued treatment for a maximum of 8 cycles. Results: Median age 54 years (range 35-67 years), Median WHO PS 0 (range 0-1). Previous adjuvant therapy anthracycline (100%) and hormone therapy (60%). Median disease free interval was 6 months. Main metastatic sites were lung (40%), liver (25%), bone (40%) skin (35%), and lymph nodes (35%). Twenty five percent of patients had one metastatic site, 60% had two sites, 10% had three sites and 5% had more than three sites. The total number of cycles delivered was 441 with a median number of cycles/patients of 7 (range 3-8). An objective tumor response was achieved in 36 pts (60%), complete response (CR) in 6 pts (10%), 12 pts (20%) had stable disease (SD). After a follow up period of 6-36 months, the median time to progression and median survival were 14 and 23 months, respectively. No WHO G4 toxicities were noted, 3 pts (5%) developed G3 neutropenia and one patient (1.7%) developed G3 hand and foot syndrome. G2 anemia, neutropenia and diarrhea were reported in 2 pts (3.3%), 3 pts (5%) and 6 pts (10%), respectively. Conclusions: The combination of vinorelbine and capecitabine showed significant efficacy and mild toxicity as a first-line treatment for patients with metastatic breast cancer after failure of adjuvant anthracycline based therapy.

Phase II trial of metronomic capecitabine and cyclophosphamide with lapatinib and trastuzumab in patients with HER2-positive metastatic breast cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e12508-e12508
Author(s):  
Irene Kang ◽  
Darcy V. Spicer ◽  
Janice M. Lu ◽  
Susan G. Groshen ◽  
Denice Tsao-Wei ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Phase Ii ◽  
Metastatic Breast ◽  
Metronomic Chemotherapy ◽  
Progression Free Survival ◽  
Median Number ◽  
Her2 Positive ◽  
Eligibility Criteria ◽  
Metastatic Setting

e12508 Background: Metronomic chemotherapy is an emerging paradigm of cancer therapy in which low doses of chemotherapy are delivered at frequent intervals. Activity in patients with metastatic breast cancer (MBC) has been demonstrated in several phase II clinical trials. Methods: We proposed a regimen with metronomic chemotherapy and dual HER2 inhibition in HER2 positive patients with MBC. We hypothesized that this regimen will be highly active in MBC and have a favorable toxicity profile. Patients were treated on a 21-day cycle with capecitabine 1500mg PO daily, cyclophosphamide 50mg daily, lapatinib 1000mg PO daily and trastuzumab 6mg/kg IV once per 21-day cycle. This regimen was continued until disease progression or unacceptable toxicity. Primary endpoint was progression free survival (PFS). Secondary endpoints were overall response rate (ORR), clinical benefit rate (CBR), overall survival (OS), and safety and tolerability of this regimen. Eligibility criteria were patients 18 years of age and older who had histologically confirmed HER2-positive metastatic breast cancer with prior trastuzumab use in the adjuvant or metastatic setting with no more than two prior regimens for MBC. Results: Ten patients were accrued from Jan 2014-Oct 2016. Median age was 52 (range 38 - 79) years. Median number of chemotherapy regimens for metastatic disease was 0.5 (range 0-2). Median PFS was 13.7 (95% CI: 2.6, 16.6) months. Median OS was 29.6 (95% CI: 11.8, 60.5+) months. ORR was 30%, and CBR was 70%. Grade 3 or 4 toxicities were identified in 6 patients. The most common toxicities of any grade were fatigue (100%), diarrhea (80%), anemia, neutropenia, ALT increase, nausea and hand-foot syndrome 50% each. One patient achieved CR for over 3 years and continues on treatment at time of this report. 8 patients progressed and 1 patient withdrew from study without response evaluation. The trial was closed due to lack of accrual. Conclusions: The proposed regimen of metronomic capecitabine and cyclophosphamide with lapatinib and trastuzumab appears to be active in patients with HER2 positive MBC but with significant toxicity. Clinical trial information: NCT01873833.

Evaluation of gemcitabine plus carboplatin in pretreated, metastatic breast cancer patients: Final analysis of a phase II trial

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1074-1074 ◽  
Author(s):  
D. Laessig ◽  
U. Vehling-Kaiser ◽  
H. J. Stemmler ◽  
P. Fasching ◽  
F. Melchert ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Median Time ◽  
Treatment Option ◽  
Phase Ii ◽  
Remission Rate ◽  
Karnofsky Performance Status ◽  
Metastatic Breast ◽  
Breast Cancer Patients

1074 Background: There is an increasing proportion of metastatic breast cancer patients (pts) who have been exposed to anthracyclines and taxanes either during perioperative treatment or during intial therapy of metastatic disease. The efficacy of gemcitabine plus cisplatin has been consistently demonstrated in several trials. This study evaluates the combination of gemcitabine plus carboplatin as a treatment option for intensively pretreated breast cancer pts. Methods: Metastatic breast cancer pts were treated with gemcitabine (1,000 mg/m2 iv on days 1 and 8) and carboplatin (AUC 4 iv on day 1) in a 3-week regimen. The trial was performed as a 2-stage phase II study according to the optimal design described by Simon (p0 = 0.1, p1 = 0.3, a = 0.05, β = 0.1) with overall remission rate (according to RECIST) as the primary objective. Results: 39 pts were recruited, median age was 60 years (29–77 yrs): median Karnofsky performance status was 90% (range, 70–100%), 77% of pts were ER- and/or PR-positive, and 28% of pts presented with Her-2 overexpression (IHC 3+ or FISH-positive). 87% of pts had visceral metastasis and 79.5% had =2 sites of metastasis. All patients had received prior chemotherapy and 92% of pts had received prior anthracyclines (87%) and/or taxanes (67%). Prior endocrine therapy had been applied to 77% of patients. Median follow-up time was 13.2 months (1–27 months) during which 207 treatment cycles were documented with a median number of 5 cycles per pt (range 1–12). A CR was observed in 1 pt, a PR in 11 pts for an overall remission rate of 31% (95%-CI: 17–48%). Stable disease was documented in 12 pts (31%) resulting in a disease control rate of 61.5%. Median time to remission was 2.6 months (1.3–5.1 months), median time to progression was 4.9 months (95%CI, 2.6–6.7 months), and overall survival was 13,2 months (95% CI, 8.7–16.7 months). Grade 3–4 leucopenia (NCI-CTC) was observed in 64%, neutropenia in 51%, thrombocytopenia in 49%, and anemia in 10% of pts. Conclusion: Gemcitabine plus carboplatin is an effective and well tolerated treatment option in intensively pretreated breast cancer pts. No significant financial relationships to disclose.

A phase II study of weekly nanoparticle albumin-bound paclitaxel combined with cisplatin in patients with metastatic breast cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e11568-e11568
Author(s):  
Biyun Wang ◽  
Xi-Chun Hu ◽  
Si Sun ◽  
Jian Zhang ◽  
Lichen Tang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Phase Ii ◽  
Overall Response Rate ◽  
Triple Negative ◽  
Response Rate ◽  
Phase Ii Study ◽  
Metastatic Breast ◽  
Primary Objective ◽  
Overall Response

e11568 Background: This prospective phase II study was to investigate the efficacy and toxicity of weekly albumin-bound paclitaxel (nab-paclitaxel) and cisplatin combination in patients with metastatic breast cancer. Methods: Females with unresectable, recurrent or metastatic breast cancer were eligible for participation. Nab-paclitaxel was administered weekly at a dose of 125 mg/m2 on d1, 8, 15, followed by cisplatin 75 mg/m2 on d1, repeated every 28 days with a maximum of 6 cycles. The primary objective was overall response rate (ORR) and the second objectives were progression free survival (PFS), safety, and overall survival (OS). Results: Seventy-three women were enrolled into this study. A total of 384 chemotherapy cycles were administered with a median of 6 cycles. A high overall response rate (67.1%) was achieved in the whole population. The highest response rate was observed in the first line patients (80.6%) and in patients who had not received taxane previously (80%). After a median follow-up of 12.8 months, the median PFS was 10.5 months. For the patients receiving first-, second- and third-line or more,median PFS was 12.3, 9.0 and 7.7 months, respectively (P=0.006). Subgroup analysis showed that the highest response rate was obtained in Her-2 positive patients, followed by patients with triple negative and luminal subtypes, yielding a response rate of 77.8%, 68.8% and 63.9%, respectively (P=0.584). The corresponding median PFS was 13.6, 12.7 and 10.0 months, respectively (P=0.83). While grade 4 neutropenia occurred in 46 patients (63.0%), febrile neutropenia occurred only in 9 patients (12.3%). Grade 3 peripheral neuropathy was an accumulated dose-limiting toxicity occurring in 19 patients (26.0%), 13 of whom had to stop chemotherapy due to no recovery to grade 2 or less within 2 weeks. Other common toxicities included alopecia, nausea, vomiting and rash. Conclusions: The results of this trial add to the clinical evidence that doublet of nab-paclitaxel and cisplatin has high efficacy and a good safety profile in treatment of patients with metastatic breast cancer. Further evaluation of this regimen in metastatic breast cancer, especially triple negative subtype, is justified.

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