Randomized Trial of 3-Hour Versus 24-Hour Infusion of High-Dose Paclitaxel in Patients With Metastatic or Locally Advanced Breast Cancer: National Surgical Adjuvant Breast and Bowel Project Protocol B-26

1999 ◽  
Vol 17 (11) ◽  
pp. 3403-3411 ◽  
Author(s):  
Roy E. Smith ◽  
Ann M. Brown ◽  
Eleftherios P. Mamounas ◽  
Stewart J. Anderson ◽  
Barry C. Lembersky ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Response ◽  
Response Rate ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
High Dose ◽  
Hematologic Toxicity ◽  
Event Free Survival ◽  
Free Survival ◽  
Grade 3

PURPOSE: Paclitaxel is an active drug for the treatment of breast cancer; however, the appropriate duration of administration is unknown. We assessed and compared the response rate, event-free survival, survival, and toxicity of paclitaxel 250 mg/m2 delivered every 3 weeks as a 3-hour or 24-hour infusion. PATIENTS AND METHODS: A total of 563 women with stage IV or IIIB breast cancer were randomized into one of two groups: 279 received 3-hour paclitaxel and 284 received 24-hour paclitaxel. Patients were stratified by age, stage of disease, and prior therapy. RESULTS: A significantly higher rate of tumor response occurred in the first four cycles of therapy in patients who received the 24-hour infusion of paclitaxel (51% v 41%, respectively; P = .025). Tumor response over all cycles was also significantly higher in the group that received 24-hour infusion (54% v 44%, respectively; P = .023). There were no significant differences in event-free survival or survival between the two arms of the study (P = .9 and .8, respectively). No treatment by stage or by age interactions were observed. During the first four cycles of therapy, at least one episode of ≥ grade 3 toxicity (excluding nadir hematologic values, alopecia, and weight change) occurred in 45% of patients who received the 3-hour paclitaxel infusion and in 50% of those who received the 24-hour paclitaxel infusion. Febrile neutropenia, ≥ grade 3 infection, and ≥ grade 3 stomatitis were less frequent, and severe neurosensory toxicity was more frequent in those who received the 3-hour paclitaxel infusion. Ten treatment-related deaths occurred in the first four cycles. Age, stage, and prior chemotherapy did not influence the effect of treatment. CONCLUSION: When administered as a continuous 24-hour infusion, high-dose paclitaxel results in a higher tumor response rate than when administered as a 3-hour infusion but does not significantly improve event-free survival or survival. Paclitaxel as a 24-hour infusion results in increased hematologic toxicity and decreased neurosensory toxicity.

Multicenter Phase II Trial of Weekly Paclitaxel in Women With Metastatic Breast Cancer

2001 ◽  
Vol 19 (22) ◽  
pp. 4216-4223 ◽  
Author(s):  
Edith A. Perez ◽  
Charles L. Vogel ◽  
David H. Irwin ◽  
Jeffrey J. Kirshner ◽  
Ravi Patel
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Phase Ii ◽  
Response Rate ◽  
Metastatic Breast ◽  
Weekly Paclitaxel ◽  
High Dose ◽  
Hematologic Toxicity ◽  
Prior Chemotherapy ◽  
Grade 3

PURPOSE: We evaluated the safety and efficacy of weekly paclitaxel therapy in women with metastatic breast cancer in a phase II multicenter trial. Entry criteria were relatively liberal to reflect the heterogeneity of metastatic breast cancer in clinical practice. PATIENTS AND METHODS: Patients had histologically confirmed and measurable metastatic breast cancer. Up to two prior chemotherapy regimens for metastatic disease, including prior therapy with anthracyclines and taxanes and prior high-dose therapy, were allowed. Paclitaxel 80 mg/m2 was administered weekly for 4 weeks per 4-week cycle. RESULTS: We enrolled 212 patients; 211 were assessable for toxicity and 177 were assessable for response. Ninety percent of patients had received prior chemotherapy (adjuvant, metastatic, or both), 46% of patients had three or more involved metastatic sites, and 60% of patients had visceral-dominant disease. Responses were documented on two occasions and were independently reviewed. The overall response rate (complete plus partial response) was 21.5% (95% confidence interval, 15.4% to 27.5%), with 41.8% of patients having disease stabilization. Median time to progression was 4.7 months, and overall survival in all 212 patients enrolled was 12.8 months. Therapy was well tolerated, with a 15% incidence of grade 3/4 hematologic toxicity and a 9% incidence of grade 3 neurotoxicity; other serious toxicities were rare. The response rate and toxicity profile in the 34% of patients ≥ 65 years of age were similar to that of younger patients. CONCLUSION: Weekly paclitaxel therapy was well tolerated and demonstrated reasonable activity in this relatively heavily pretreated population with advanced disease. Further study of weekly paclitaxel in combination therapy is warranted.

A Phase II Study of Carfilzomib, Pegylated Liposomal Doxorubicin, and Dexamethasone for Relapsed or Refractory Multiple Myeloma

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3329-3329 ◽  
Author(s):  
Mark A Fiala ◽  
Jesse Keller ◽  
Jeevan Sekhar ◽  
Connie Ceriotti ◽  
Camille N. Abboud ◽  
...  
Keyword(s):  
Research Funding ◽  
Overall Response Rate ◽  
Response Rate ◽  
Pegylated Liposomal Doxorubicin ◽  
Median Number ◽  
Hematologic Toxicity ◽  
Event Free Survival ◽  
Free Survival ◽  
Overall Response ◽  
Grade 3

Abstract Background: We previously reported on a phase I dose escalation trial of CDD [carfilzomib (CFZ), pegylated liposomal doxorubicin (PLD), and dexamethasone (DEX)] (Keller, et, al, ASH 2014 Abstract 4731). The combination was well tolerated and an MTD was not reached despite administering the currently approved single-agent doses. In the maximum dose level tested, the overall response rate (ORR) was 72% (5/7) in a heavily pre-treated population. Based on the promising results of the phase I study we conducted a phase II expansion to further evaluate the efficacy of the regimen. Patient/Methods: Patients with RRMM after ≥ 1 lines of therapy, with measureable disease, and good performance status, organ function and hematological reserve were eligible. Prior CFZ or PLD/doxorubicin exposure was permitted. CFZ was given on days 1, 2, 8, 9, 15 and 16 in 28 day cycles at a dose of 56mg/m2, PLD on day 8 at a dose of 30mg/m2,DEX on days 1, 2, 8, 9, 15 and 16 at a dose of 20mg. Following 6 cycles of combination therapy, PLD was discontinued and patients were treated with maintenance CFZ and DEX (once weekly). Response was assessed per IMWG criteria. Overall response rate (ORR) was defined as partial response (PR) or better, event-free survival as the interval from start of therapy to discontinuation. Results: Twenty-three patients were enrolled from April 2014-Mar 2016. Median age was 63 years (range 27-70) and 52% were male. Ten patients were ISS stage 1, 6 were stage 2, and 7 were stage 3. By mSMART criteria, 1 patient was high risk and 5 were intermediate risk. Ten patients were IgG Kappa subtype; 4 had IgG Lambda subtype, 2 had IgA Kappa subtype, 2 had IgA Lambda subtype, 3 kappa light chain, and 2 lambda light chain. The median number of prior therapies was 2 (range 1-13); median time from diagnosis to start of protocol was 40 months (range 8-200). All had prior exposure to lenalidomide; 91% to bortezomib; 9% to PLD or doxorubicin; 9% to CFZ; 96% had undergone autologous transplantation. The overall response rate was 83% with 48% achieving a complete or very good partial response. The median number of cycles was 11; the median estimated event-free survival was 7.4 months at a median follow-up of 10.6 months. Five patients discontinued due to disease progression, 7 due to toxicity, 1 to proceed to a second transplant, and 10 remain on treatment at time of submission. Individual patient responses are summarized in Table 1. Grade 3/4 non-hematologic toxicity was uncommon but included: infections (11), hypertension (4), RPLS (1), and MI (1). Grade 3/4 hematologic toxicity included: thrombocytopenia (11), anemia (8), neutropenia (7), TTP (1), and hemolysis (1). Conclusion: CDD is well tolerated and efficacious in relapsed or refractory MM. The estimated ORR of the combination is 83% (95% CI 67%-98%) a notable increase compared to standard dose CFZ and DEX. Disclosures Abboud: Gerson and Lehman Group: Consultancy; Baxalta: Honoraria; Takeda: Honoraria; Novartis: Research Funding; Seattle Genetics: Research Funding; Alexion: Honoraria; Cardinal: Honoraria; Teva: Research Funding, Speakers Bureau; Pharmacyclics: Honoraria; Pfizer: Research Funding; Merck: Research Funding. DiPersio:Incyte Corporation: Research Funding. Vij:Amgen: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Celgene: Consultancy; Bristol-Myers Squibb: Consultancy; Janssen: Consultancy; Shire: Consultancy; Jazz: Consultancy; Karyopharma: Consultancy; Novartis: Consultancy.

scholarly journals Assessment and Prediction of Response to Neoadjuvant Chemotherapy in Breast Cancer: A Comparison of Imaging Modalities and Future Perspectives

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3521
Author(s):  
Valeria Romeo ◽  
Giuseppe Accardo ◽  
Teresa Perillo ◽  
Luca Basso ◽  
Nunzia Garbino ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Tumor Response ◽  
Imaging Techniques ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Complete Response ◽  
Mri Imaging ◽  
Future Perspectives ◽  
Advanced Imaging

Neoadjuvant chemotherapy (NAC) is becoming the standard of care for locally advanced breast cancer, aiming to reduce tumor size before surgery. Unfortunately, less than 30% of patients generally achieve a pathological complete response and approximately 5% of patients show disease progression while receiving NAC. Accurate assessment of the response to NAC is crucial for subsequent surgical planning. Furthermore, early prediction of tumor response could avoid patients being overtreated with useless chemotherapy sections, which are not free from side effects and psychological implications. In this review, we first analyze and compare the accuracy of conventional and advanced imaging techniques as well as discuss the application of artificial intelligence tools in the assessment of tumor response after NAC. Thereafter, the role of advanced imaging techniques, such as MRI, nuclear medicine, and new hybrid PET/MRI imaging in the prediction of the response to NAC is described in the second part of the review. Finally, future perspectives in NAC response prediction, represented by AI applications, are discussed.

Randomized Phase II Trial of First-Line Trastuzumab Plus Docetaxel and Capecitabine Compared With Trastuzumab Plus Docetaxel inHER2-Positive Metastatic Breast Cancer

2010 ◽  
Vol 28 (6) ◽  
pp. 976-983 ◽  
Author(s):  
Andrew M. Wardley ◽  
Xavier Pivot ◽  
Flavia Morales-Vasquez ◽  
Luis M. Zetina ◽  
Maria de Fátima Dias Gaui ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Response Rate ◽  
Performance Status ◽  
Locally Advanced ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
First Line ◽  
Her2 Positive ◽  
Grade 3

PurposeTo evaluate trastuzumab (H) and docetaxel (T) with or without capecitabine (X) as first-line combination therapy for human epidermal growth factor receptor 2 (HER2) -positive advanced breast cancer.Patients and MethodsPatients with HER2-positive locally advanced or metastatic breast cancer were randomly assigned to H (8 mg/kg loading; 6 mg/kg every 3 weeks) plus T (75 mg/m2in HTX arm, 100 mg/m2in HT arm, every 3 weeks) with or without X (950 mg/m2twice per day on days 1 to 14 every 3 weeks). The primary end point was overall response rate (ORR).ResultsIn 222 patients, median follow-up was approximately 24 months. ORR was high with both regimens (70.5% with HTX; 72.7% with HT; P = .717); complete response rate was 23.2% with HTX compared with 16.4% with HT. HTX demonstrated significantly longer progression-free survival: median 17.9 months compared with 12.8 months with HT (hazard ratio, 0.72; P = .045), which translates to a gain of around 5 months. Two-year survival probability was 75% with HTX compared with 66% with HT. Febrile neutropenia (27% v 15%) and grade 3/4 neutropenia (77% v 54%) incidences were higher with HT than HTX. Treatment-related grade 3 hand-foot syndrome (17% v < 1%) and grade 3/4 diarrhea (11% v 4%) occurred more commonly with HTX than HT. One case of congestive heart failure occurred in each arm.ConclusionHTX is an effective and feasible first-line therapy for HER2-positive locally advanced or metastatic breast cancer, although it should be reserved for patients with good performance status who are not receiving long-term steroids.

scholarly journals A Phase II Study of Sequential Treatment with Anthracycline and Taxane Followed by Eribulin in Patients with HER2-negative, Locally Advanced Breast Cancer (JBCRG-17)

2021 ◽  
Author(s):  
Ippei Fukada ◽  
Yoshinori Ito ◽  
Naoto Kondo ◽  
Shoichiro Ohtani ◽  
Masaya Hattori ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Clinical Response ◽  
Phase Ii ◽  
Response Rate ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Advanced Breast ◽  
Clinical Response Rate ◽  
Sequential Administration

Abstract PurposeThe sequence of taxanes (T) followed by anthracyclines (A) as neoadjuvant chemotherapy (NAC) has been the standard of care for almost 20 years for locally advanced breast cancer (LABC). Sequential administration of eribulin (E) following A/T could provide a greater response rate for women with LABC.MethodsIn this single-arm, multicenter, Phase II prospective study, the patients received 4 cycles of the FEC regimen and 4 cycles of taxane. After the A/T-regimen, 4 cycles of E were administered followed by surgical resection. The primary endpoint was the clinical response rate. Eligible patients were women aged 20 years or older, with histologically confirmed invasive breast cancer, clinical Stage IIIA (T2-3 and N2 only), Stage IIIB, and Stage IIIC, HER2-negative.ResultsA preplanned interim analysis aimed to validate the trial assumptions was conducted after treatment of 20 patients and demonstrated that clinical progressive disease (cPD) rates in the E phase were significantly higher (30%) than assumed. Therefore, the Independent Data Monitoring Committee recommended stopping the study. Finally, 53 patients were enrolled, and 26 patients received the A/T/E-regimen. The overall observed clinical response rate (RR) was 73% (19/26); RRs were 77% (20/26) in the AT phase and 23% (6/26) in the E phase. Thirty percent (8/26) of patients had PD in the E phase, 6 of whom had achieved cCR/PR in the AT phase. Reported grade >3 AEs related to E were neutropenia (42%), white blood cell count decrease (27%), febrile neutropenia (7.6%), weight gain (3.8%), and weight loss (3.8%)ConclusionSequential administration of eribulin after the A/T-regimen provided no additional effect for LABC patients. Future research should continue to focus on identifying specific molecular biomarkers that can improve response rates.

scholarly journals Experimental, Clinical, and Morphological Analysis of H-Ras Oncoproteins for Locally Advanced Breast Cancer

2020 ◽  
Vol 8 (B) ◽  
pp. 1077-1082
Author(s):  
Ainura Maratovna Zhumakayeva ◽  
K. D. Rakhimov ◽  
I. M. Omarova ◽  
S. M. Adekenov ◽  
S. S. Zhumakayeva
Keyword(s):  
Breast Cancer ◽  
Comparative Analysis ◽  
Neoadjuvant Chemotherapy ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Survival Rates ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Positive Expression ◽  
Egfr Expression

BACKGROUND: Activated forms of RAS increase both in breast cancer and in cell lines in the presence of estimated glomerular filtration rate (EGFR) or HER2 expression. HRAS oncoproteins play an important role in enhancing the proliferation and resistance of breast cancer tumor cells to apoptosis. A number of studies have shown a significant decrease in EGFR expression after neoadjuvant chemotherapy, which has been clinical, manifested by an improvement in immediate efficacy and an increase in overall and relapse-free breast cancer survival rates. AIM: The aim of the study was to study relapse-free survival depending on the expression of the H-RAS oncoprotein in patients with breast cancer who received different treatment regimens for the farnesyltransferase inhibitor. METHODS: H-RAS status was assessed by immunohistochemistry. RESULTS: A comparative analysis of patients with negative expression of H-RAS oncoproteins showed a statistically significant increase in relapse-free survival in the subgroups who received neoadjuvant chemotherapy according to the AC regimen (adriablastin + cyclophosphamide) and AC + arglabin, compared with monotherapy by arglabin: Kruskal–Wallis= 12.56, where p = 0.001. A comparative analysis of patients with positive expression of H-RAS showed that in the subgroups treated with arglabin and AC+arglabin, there was a statistically significant increase in relapse-free survival compared with the AC subgroup: Kruskal–Wallis = 10.96, where p = 0.004. It was established that the positive expression of H-RAS negatively affects not only the direct effectiveness of neoadjuvant therapy but also worsens the rates of relapse-free survival. However, in patients with positive H-RAS expression who received arglabin in monotherapy, there was a statistically significant increase in relapse-free survival up to 16.5 ± 1.1 months compared with the standard AC regimen (13.5 ± 1.1 months) (р ˂ 0.05), the addition of arglabin to the standard AC regime also increased this indicator to 16.4 ± 1.2 months (р ˂ 0.05). CONCLUSION: These results may indicate the clinical applicability of determining H-RAS as a prognostic factor for relapse-free survival in breast cancer.

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