Dose-dense (DD) cyclophosphamide, methotrexate, and fluorouracil (CMF) at 14-day intervals: A pilot study of every 14- and 10–11-day dosing intervals for women with early-stage breast cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 590-590
Author(s):  
P. Drullinsky ◽  
M. N. Fornier ◽  
S. Sugarman ◽  
G. D'Andrea ◽  
T. Troso-Sandoval ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Stage ◽  
Early Stage Breast Cancer ◽  
Hematologic Toxicity ◽  
Type I ◽  
Initial Cohort ◽  
Grade 3 ◽  
Dose Dense ◽  
Q 14 ◽  
Dosing Intervals

590 Background: CMF (C 600 mg/m2, M 40 mg/m2, F 600 mg/m2) is an option for adjuvant therapy for patients with low risk early stage breast cancer. DD regimens as predicted by mathematical models of cancer growth and treatment response are superior. We previously demonstrated the safety of DD EC (epirubicin/cyclophosphamide) followed by paclitaxel at 10–11 day (d) intervals. We investigated the feasibility of administering DD adjuvant CMF every 14 d and then every 10–11 d in a 2-stage phase II trial. Methods: An initial cohort (A) was treated q 14 d with PEG-filgrastim (Neulasta) support. A second cohort (B) was treated every 10–11 d with filgrastim/Neupogen x 5 d and then, based on feasibility, modified (cohort C) to use 7 d filgrastim. The primary end point was feasibility defined as having ANC > 1.5 x 103/uL on day 1 of planned treatment for all 8 cycles with no grade 3 or higher non-hematologic toxicity. All three cohorts were tested using a Simon's two-stage optimal design with type I and type II errors set at 10%. This design would effectively discriminate between true tolerability (as protocol-defined) rates of< 60% and> 80%. Cohort A: 38 pts with early stage breast cancer were accrued from 3/2008 though 6/2008. Cohort B: 7 pts were accrued from June 2008 through August 2008. Cohort C: Is still open with 16 pts accrued from August 2008 through December 5, 2008. Results: Median age 51: range 38 to 78. Cohort A: 29/38 pts completed 8 cycles of CMF. The regimen was considered feasible. 2 other pts completed 7 cycles and were withdrawn for depression and grade 2 transaminitis. The 7 other pts completed between 1 and 6 cycles of CMF were withdrawn as follows: 3 personal, 1 (grade 3) bone pain, 2 allergy unrelated to CMF, and 1 seizure. Cohort B: 7 pts were accrued. 6 out of 7 pts could not complete 8 cycles of chemotherapy secondary to neutropenia and 1 secondary to grade 3 ALT elevation. Cohort C: Accrual has not been completed. 16 pts are currently enrolled. Conclusions: Dose dense adjuvant CMF is feasible at 14 d intervals with PEG-filgrastim support. Adjuvant CMF every 10–11 days with filgrastim given for 5 days beginning day 2 is not feasible. Accrual is ongoing for CMF at 10–11 days with filgrastim x 7 days. Updated results will be available for Cohort C. [Table: see text]

scholarly journals Definitive Results of a Phase III Adjuvant Trial Comparing Three Chemotherapy Regimens in Women With Operable, Node-Positive Breast Cancer: The NSABP B-38 Trial

2013 ◽  
Vol 31 (26) ◽  
pp. 3197-3204 ◽  
Author(s):  
Sandra M. Swain ◽  
Gong Tang ◽  
Charles E. Geyer ◽  
Priya Rastogi ◽  
James N. Atkins ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Stage ◽  
Disease Free Survival ◽  
Sensory Neuropathy ◽  
Early Stage Breast Cancer ◽  
Phase Iii ◽  
Node Positive ◽  
Grade 3 ◽  
Dose Dense ◽  
Positive Breast Cancer

Purpose Anthracycline- and taxane-based three-drug chemotherapy regimens have proven benefit as adjuvant therapy for early-stage breast cancer. This trial (NSABP B-38; Combination Chemotherapy in Treating Women Who Have Undergone Surgery for Node-Positive Breast Cancer) asked whether the incorporation of a fourth drug could improve outcomes relative to two standard regimens and provided a direct comparison of those two regimens. Patients and Methods We randomly assigned 4,894 women with node-positive early-stage breast cancer to six cycles of docetaxel, doxorubicin, and cyclophosphamide (TAC), four cycles of dose-dense (DD) doxorubicin and cyclophosphamide followed by four cycles of DD paclitaxel (P; DD AC→P), or DD AC→P with four cycles of gemcitabine (G) added to the DD paclitaxel (DD AC→PG). Primary granulocyte colony-stimulating factor support was required; erythropoiesis-stimulating agents (ESAs) were used at the investigator's discretion. Results There were no significant differences in 5-year disease-free survival (DFS) between DD AC→PG and DD AC→P (80.6% v 82.2%; HR, 1.07; P = .41), between DD AC→PG and TAC (80.6% v 80.1%; HR, 0.93; P = .39), in 5-year overall survival (OS) between DD AC→PG and DD AC→P (90.8% v 89.1%; HR, 0.85; P = .13), between DD AC→PG and TAC (90.8% v 89.6%; HR, 0.86; P = .17), or between DD AC→P versus TAC for DFS (HR, 0.87; P = .07) and OS (HR, 1.01; P = .96). Grade 3 to 4 toxicities for TAC, DD AC→P, and DD AC→PG, respectively, were febrile neutropenia (9%, 3%, 3%; P < .001), sensory neuropathy (< 1%, 7%, 6%; P < .001), and diarrhea (7%, 2%, 2%; P < .001). Exploratory analyses for ESAs showed no association with DFS events (HR, 1.02; P = .95). Conclusion Adding G to DD AC→P did not improve outcomes. No significant differences in efficacy were identified between DD AC→P and TAC, although toxicity profiles differed.

Optimizing dose-dense regimens for early-stage breast cancer

2010 ◽  
Vol 7 (12) ◽  
pp. 678-679 ◽  
Author(s):  
Patrick G. Morris ◽  
Clifford A. Hudis
Keyword(s):  
Breast Cancer ◽  
Early Stage ◽  
Early Stage Breast Cancer ◽  
Dose Dense

Safety and effectiveness of dose dense neoadjuvant chemotherapy in patients with stage II/III breast cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10622-10622
Author(s):  
S. A. McDaniel ◽  
H. Krontiras ◽  
J. T. Carpenter ◽  
L. M. Nabell ◽  
K. I. Bland ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Residual Disease ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Hematologic Toxicity ◽  
Newly Diagnosed ◽  
Grade 3 ◽  
Dose Dense ◽  
To Receive

10622 Background: NSABP B-18 randomized women with operable breast cancer to receive chemotherapy either pre- or postoperatively; OS and DSF rates at 9 years were identical. Importantly, pathologic complete response (pCR) was directly proportional to DFS and OS. Recently, dose dense adjuvant chemotherapy has shown a statistically significant improvement in DFS and OS. However, no data is available for the use of dose dense preoperative chemotherapy at this time. Methods: Women enrolled in the I-SPY correlative trial with newly diagnosed breast cancer, T ≥ 3cm, any N, M0 were evaluated to assess response rates and safety to dose dense neoadjuvant chemotherapy (doxorubicin 60 mg/m2 IV Q2 wks × 4, paclitaxel 175 mg/m2 IV Q2 wks × 4, and cyclophosphamide 600 mg/m2 IV Q2 wks × 4). Results: Since 02/2003, 43 pts have been treated with dose dense neoadjuvant chemotherapy on the I-SPY trial at UAB (mean age 47.9). 47% of the pts were ER+, 37% were PR+ and 5% were Her2+ by FISH. 2 pts dropped out for personal reasons and 9 pts are actively undergoing treatment. Overall, 32 pts received dose dense chemotherapy and proceeded to surgery. Of those, 31 received dose dense sequential ATC and 1 received dose dense concurrent AC followed by T. 34% had a pCR (breast & nodes) while an additional 10% had a pCR in the breast but residual disease in lymph nodes; 41% had a PR; 9% had SD; and 6% had PD. Hematologic toxicity consisted of grade 3 anemia in 2 pts, febrile neutropenia in 2 pts and no grade 4 thrombocytopenia. Non-hematologic grade 3–4 toxicity consisted of mediport-associated thrombosis in 2 pts, hyperglycemia in 2 pts, syncope in 1 pt, neuropathy in 1 pt, and disseminated varicella in 1 pt. Conclusion: Our results show that dose dense neoadjuvant chemotherapy achieves a pCR (breast & nodes) in about 1/3 of patients (34%) with tolerable toxicity. No significant financial relationships to disclose.

Review of trends in adjuvant chemotherapy regimens in breast cancer over 10 year period at Yale New Haven Hospital (YNHH).

2015 ◽  
Vol 33 (28_suppl) ◽  
pp. 144-144
Author(s):  
Rosana Gnanajothy ◽  
Gina G. Chung ◽  
Michael DiGiovanna ◽  
Maysa M. Abu-Khalaf ◽  
Donald R. Lannin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Chemotherapy ◽  
Triple Negative ◽  
Early Stage ◽  
Retrospective Chart Review ◽  
Early Stage Breast Cancer ◽  
New Haven ◽  
Prescribing Trends ◽  
Her 2 ◽  
Dose Dense

144 Background: Adjuvant chemotherapy for breast cancer has undergone many changes over the past 10 yrs. The objective of the study was to review prescribing trends in adjuvant chemotherapy regimens for early stage breast cancer in a single institution, over a decade. Methods: A retrospective chart review was conducted of patients (pts) with early stage breast cancer treated at YNHH from 2002 to 2011.Total charts analyzed was 1097 and 308 pts had complete data. Results: The HER 2 positive group accounted for 64 pts. The most commonly used regimen was ACTH (doxorubicin and cyclophosphamide 4-14 d cycles, paclitaxel and trastuzumab weekly for 12 weeks, and trastuzumab for 1 yr). This regimen was utilized in 35% of pts and was most likely to be used in node positive (N+ve) pts compared to node negative (N-ve) pts (OR 2.9 (95 % CI 0.97-9.1)).TCH (docetaxel, carboplatin, trastuzumab,6-21 d cycles and trastuzumab for 1 year) was the second most common regimen used in 21% of pts and predominantly in N-ve pts(OR 12.4 (95% CI 02.45-63.2)). Majority of the study group (184 pts) were ER+PR+ and HER 2- .The predominant chemo regimen was DD AC T (dose dense AC followed by paclitaxel in 4 -14d cycles each) in 50% of pts, and TC (Docetaxel, cyclophosphamide4-21d cycles) utilized in 48 pts (26.09 %). Majority of the N-ve pts were treated with TC (OR 12.4(95% CI 2.4-63.27) whereas N+ve pts were predominately treated with DDACT (OR 2.98(95% CI 0.97-9.16). The Triple negative group included a total of 57 pts .The most frequent chemo regimen through the years was DDACT (54.39% of pts) followed by TC (21.05% of pts). N+ve pts were more likely to be treated with DDACT (OR 8.91(95% CI (2.65-29.94)) whereas N-ve pts mostly received TC (OR 8.75(95% CI (1.70-45.00)) The methotrexate and 5 fluorouracil based regimens were utilized more frequently in earlier years of study and less frequently in later years. Conclusions: Anthracycline and taxane based regimens have gained precedence over older regimens. HER 2 +ve pts were most commonly treated with ACTH, and TCH. N+ve HER 2+ pts were most likely to be treated with ACTH and N-ve HER2+ pts with TCH. In Her 2 negative and triple negative pts, DDACT was more utilized in N+ve pts whereas, TC regimen in the N-ve pts.

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