AC Regimen

Abstract: The increasing number of breast cancer survivors makes the issues of ovarian dysfunction and childbearing ability more and more relevant for the quality of life of these patients. The incidence of ovarian dysfunction is related to patient age, the specific agents used and the total dose administered, especially the dose of alkylating agents such as cyclophosphamide. Amenorrhea rates following combination chemotherapy consisting of cyclophosphamide + methotrexate + 5-flurouracil (CMF regimen) range from 21 to 71% in women aged 40 years and younger, and from 40 to 100% in older ones. In most series anthracycline-based adjuvant chemotherapy regimens appear to have a lower incidence of amenorrhea, which is probably due to the lower cumulative cyclophosphamide dose administered compared with that given in the CMF regimen. Few data are currently available regarding ovarian function in women treated with taxane-based chemotherapy. In a recent retrospective study on 191 patients, the amenorrhea rate was 64% for women who received doxorubicin + cyclophosphamide (AC regimen) followed by a taxane, compared with 55% (p = 0.05) for those treated with AC alone. Forty percent of women aged 40 years or younger resumed menstruation, whereas the amenorrhea was more likely to be irreversible in older women; however, the addition of a taxane did not change the reversibility rate. Ovarian reserve can be tested with serum assays of follicle-stimulating hormone, inhibin B, estradiol and anti-Mullerian hormone, as well as by ultrasound assessment of antral follicle count. A review of literature data failed to show that a subsequent pregnancy increases the risk of recurrence and death in breast cancer survivors, and some series have even detected longer survival for patients who get pregnant after breast cancer treatment. This apparent survival benefit, probably due to a selection bias called the 'healthy mother effect', suggests that breast cancer survivors who subsequently conceive are a self-selecting group of women with better prognosis. The little available information appears to show no increase in the incidence of prematurity, stillbirth or congenital malformations in their babies. In conclusion, future pregnancy is a viable option for a woman treated for early-stage breast cancer and does not appear to be detrimental to either the mother or her offspring.

Abstract: The aim of this study was to investigate the incidence of febrile neutropenia (FN) with adjuvant AC (doxorubicin and cyclophosphamide) chemotherapy among Asian early-stage breast cancer (ESBC) patients, to evaluate the impact of FN on chemotherapy delivery, and to identify specific risk factors that would predispose ESBC patients to FN. This was a single-center, observational, retrospective cohort study conducted in Singapore. All ESBC patients who have received the AC regimen as adjuvant chemotherapy between January 2007 and July 2010 were included into the study. Patients did not receive granulocyte colony-stimulating factors (G-CSF) as primary prophylaxis. One hundred and eighty-nine patients and 729 cycles of chemotherapy were analyzed in this study, of which, majority were Chinese (84%). Median age of the patients was 54 years old (IQR 49–58). In total, 26 patients (13.8%) manifested at least one episode of FN, of which 17 patients developed FN during the first cycle of treatment. Patients who manifested FN received similar dose intensities of chemotherapy, compared to those patients who did not manifest FN (100% versus 98%, p = 0.95). After adjusting for age, race, and presence of comorbidities, low body mass index (BMI) (<23 kg/m2) was found to be associated with a higher risk of FN (OR 4.4, 95% CI = 1.65–12.01, p = 0.003). Asian patients are at moderate risk for FN when they receive the AC regimen for treatment of ESBC. Further studies should evaluate the role of G-CSF to reduce the occurrence of FN in Asian patients with low BMI.

Abstract: Background and Aim: A proton pump inhibitor (PPI)-based triple therapy consisting of a PPI, amoxicillin (A) and clarithromycin (C) or metronidazole (M) provides an eradication rate ranging from 80 to 90%. However, there have been few controlled studies with regard to the most effective regimen to re-treat patients after failure of the first-line therapy. Accordingly, we retrospectively reviewed our experiences and compared regimens with different combinations of antimicrobials to determine the optimal retreatment regimen. Methods: Out of 133 patients who had received second-line therapy after failure of first-line PPI/AC therapy, we selected, for review, patients who took the prescribed drugs for first-line therapy equal to, or more than 80%. As a result, data on 114 patients (83 males and 31 females; mean age 49.1 ± 13.0 years; peptic ulcer n = 89; non-ulcer dyspepsia, n = 25) were eligible for evaluation. They had either repeated the PPI/AC regimen (n = 34; 5–14 days), or had been administered the PPI/AM regimen (n = 80; 10 days). The cure rates of the two regimens were compared. Results: The eradication rates for second-line therapy with the PPI/AC regimen versus the PPI/AM regimen were 52.9% (95% CI, 35–70) versus 81.3% (95% CI, 71–89) by intention-to-treat analysis (P < 0.01), and 62.1% (95% CI, 42–79) versus 91.4% (95% CI, 81–97) by per-protocol analysis (P < 0.01). Conclusion: The eradication rate for the PPI/AM retreatment regimen was significantly higher than for the repeated PPI/AC regimen, suggesting that a 10-day PPI/AM regimen can be recommended as a retreatment regimen for patients who had first-line eradication therapy by PPI/AC regimens.

Abstract: Anthracyclines (including doxorubicin) are still the backbone of commonly used breast cancer chemotherapy regimens Despite increasing use of doxorubicin and cyclophosphamide (AC) combinations for treating breast cancer, their potential to cause adverse skeletal effects remains unclear This study examined the effects of treatments with the AC regimen on bone and bone marrow in adult female rats AC treatment for four cycles (weekly intravenous injection of 2 mg/kg doxorubicin and 20 mg/kg cyclophosphamide) resulted in a reduced volume of trabecular bone at the metaphysis, which was associated with reduced serum levels of 25-hydroxy vitamin D3 and alkaline phosphatase Reductions in densities of osteocytes and bone lining cells were also observed In addition, bone marrow was severely damaged, including a severe reduction in bone marrow cellularity and an increase in marrow adipocyte content Accompanying these changes, there were increases in mRNA expression of adipogenesis regulatory genes (PPARγ and FABP4) and an inflammatory cytokine (TNFα) in metaphysis bone and bone marrow This study indicates that AC chemotherapy may induce some bone loss, due to reduced bone formation, and bone marrow damage, due to increased marrow adiposity Preventive strategies for preserving the bone and bone marrow microenvironment during anthracycline chemotherapy warrant further investigation