Fluorouracil, Doxorubicin And Cyclophosphamide Research Articles

PROSPECTIVE STUDY TO COMPARE CLINICAL, PATHOLOGICAL RESPONSE AND ACUTE TOXICITIES IN PACLITAXEL, DOXORUBICIN AND CYCLOPHOSPHAMIDE (PAC) REGIME VERSUS 5-FLUOROURACIL, DOXORUBICIN AND CYCLOPHOSPHAMIDE (FAC) REGIME AS NEO-ADJUVANT CHEMOTHERAPY IN PATIENTS WITH LOCALLY ADVANCED BREAST CANCER.

Background: Treatment outcome and prognosis of patients with locally advanced breast cancer is poor due to higher rate of relapse despite of advanced treatment protocol. Neo-adjuvant chemotherapy helps to down stage the large size tumor and also arrests micro-metastasis in the earliest. Pathological complete response after neo-adjuvant chemotherapy showed better long term survival. The aim of our study was to compare clinical and pathological response and acute toxicities in Paclitaxel, doxorubicin and cyclophosphamide (PAC) regime versus Fluorouracil, doxorubicin and cyclophosphamide (FAC) regime as neo-adjuvant chemotherapy in patients with locally advanced breast cancer. Materials And Methods: Locally advanced Invasive ductal carcinoma of breast of female patients were included in our study. All patients received median 4 cycles of neo-adjuvant chemotherapy. 20 patients in Control group received FAC regimen: Injection 5-Fluorouracil 500mg/m2, Doxorubicin 50mg/m2, Cyclophosphamide 500mm/m2 in D1. 20 patients in Study group received PAC regimen: Injection Paclitaxel 175mg/m2, doxorubicin 50mg/m2, Cyclophosphamide 500mg/m2 in D1. Results: Complete clinical response was 10% in control group (FAC regime) and 30% in study group (PAC regime). Complete pathological response was more in PAC regime group (25%) compare to FAC regime group (10%). In our study grade 1 and 2 toxicities developed which were manageable but there was no grade ¾ toxicities. Conclusion: PAC regime showed higher rate of complete clinical and pathological response with acceptable acute toxicities compare to FAC regime in locally advanced breast cancer patients.

To Evaluate the Changes Arise in the Parameters of Liver and Kidney during Adjuvant Chemotherapy in Breast Cancer Patients

To find out the variation in basic parameters of liver and kidney during FAC or CAF adjuvant chemotherapy in breast cancer patients at NIMRA jamshoro. A follow up study conducted at Nuclear, Institute of Medicine Radiotherapy (NIMRA), Jamshoro, Sindh, Pakistan. Our findings include the variations in the level of Total bilirubin, Alkaline phosphotae and Alanine transaminase as the parameters of liver. The mean±SD of total bilirubin before FAC (5-Fluorouracil, doxorubicin and cyclophosphamide) or CAF (Cyclophosphamide, doxorubicin and 5-Fluorouracil) Adjuvant Chemotherapy in Breast Cancer Patients was 0.76±0.23 and after it was 1.23±0.16. The mean±SD of Alkaline phosphatase before FAC or CAF Adjuvant Chemotherapy in Breast Cancer Patients was 96.2±2.89 and after it was 131±14.3 and Alanine tranaminase before FAC or CAF Adjuvant Chemotherapy the mean±SD was 25.5±6.18 and after it becomes 37.7±5.18. we found the variations in the level of urea and creatinine as the parameters of kidney. The mean±SD of urea and creatinine before FAC or CAF Adjuvant Chemotherapy in Breast Cancer Patients was 15.4±4.98 and 0.85±0.20 and after chemotherapy they were 28.0±1.70 and 1.76±0.09 respectively. The main parameters of liver and kidney were statistical signi cantly increased after the FAC or CAF adjuvant chemotherapy in the woman with breast cancer. These changes will alter the working of these organs put drastic effects on the normal metabolic and excretory function of liver and kidney.

Quality of Life of Breast Cancer Women During Chemotherapy with Fluorouracil, Doxorubicin and Cyclophosphamide (FAC) Regimen

Objective: To assess quality of life (QoL) of female breast cancer patients undergoing chemotherapy with a fluorouracil, doxorubicin, and cyclophosphamide (FAC) regimen.Material and Method: This prospective analytical study was performed among 40 Thai female patients receiving the FAC regimen at Pranangklao Hospital, Nonthaburi province. Their QoL was assessed using the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and Breast Cancer Module (EORTC QLQ-BR23).Results: Most patients were aged 50 years or over (77.5%) and had been diagnosed with stage 2 breast cancer (47.5%). According to the EORTC QLQ-C30, the patients’ QoL significantly decreased compared to the baseline after cycle 3 for global health status (p-value=0.002) and QoL (p-value=0.001), as well as physical functioning (p-value=0.015) and role functioning (p-value=0.001), while symptoms of fatigue, nausea/vomiting, and appetite loss increased (p-value<0.001). After cycle 5, the patients’ QoL was still significantly lower than at baseline, for physical functioning (p-value=0.009) and symptoms of fatigue, nausea/vomiting, appetite loss (p-value<0.001) and dyspnea (p-value=0.005). The EORTC QLQ-BR23 reported significantly worse systemic therapy side effects for both cycles 3 and 5 (p-value<0.001), and distress due to hair loss also appeared after cycle 5 (p-value=0.016). No significant differences were revealed on any scales between cycles 3 and 5.Conclusion: The patients’ QoL significantly decreased after chemotherapy with the FAC regimen, with some side effects from treatment and reduction in some functioning.

Response to neoadjuvant chemotherapy in operable breast carcinoma and conversion of modified radical mastectomy to breast conservation surgery, long term results: an Indian perspective

Background: This was a prospective study conducted in a tertiary care hospital over a period of one year w.e.f 01.09.06 to 31.08.07 and included 25 female breast cancer patients who were fine needle aspiration cytology proven. The objective of this study was to observe the response to neoadjuvant chemotherapy (NACT) in T1-T3, N0-N1, M0 patients and to determine the % of patients on whom breast conservation surgery could be performed. Majority of the patients were in 5th or 6th decades of life.Methods: Thorough clinical examination, bilateral mammography and ultrasound of the diseased breast was performed before administering CAF (cyclophosphamide, doxorubicin and 5-Fluorouracil) based NACT. Majority of the patients received three cycles of NACT. All patients tolerated the treatment well without any severe adverse effects.Results: Overall 84% of the patients showed response to NACT with 12% showing complete clinical regression of the primary tumour. The incidence of clinically negative axilla increased from 20% to 48% after NACT. The breast conservation surgery (BCS) rate increased from 12% to 64% after NACT.Conclusions: Of 16 patients who had undergone BCS, one patient had ipsilateral breast recurrence at four years and another one at six years of follow up; that proves the importance and success of BCS in carefully selected patients in our setup.

Chemotherapy alters cisatracurium induced neuromuscular blockade characteristics: A prospective cohort study

Study objectiveTo compare the characteristics of NMDR induced muscle paralysis in breast cancer patients with and without a history of recent chemotherapy with cyclophosphamide, doxorubicin and 5-fluorouracil (CAF) regimen. DesignThis is a non-randomized prospective cohort study. SettingOperating room of a university-affiliated teaching hospital. PatientsOut of a total of 50 patients who had undergone mastectomy, 22 patients were allocated to the “Chemo group” and 28 patients to the “Non-Chemo group”, based on a valid history of recent chemotherapy. InterventionAfter induction of anesthesia with thiopental and cisatracurium, neuromuscular monitoring was started for all patients. MeasurementsInitially the time to 100% single-twitch (ST) suppression was measured. Then, the time for the appearance of the first response to post-tetanic count (PTC) stimulation, Train-of-Four (TOF) stimulation, and TOF50% were measured consequently. Main resultsTime to get STzero was significantly longer in the Chemo group than in the Non-chemo group. Time for the appearance of the first response of PTC and TOF and TOF50% was significantly shorter in the Chemo group than the other group. The mean duration of intense block was 27.66 minutes in the Chemo group versus 42.47 minutes in the Non-chemo group. ConclusionThis research demonstrated that in patients having undergone chemotherapy, the effect of NDMRs starts with a longer lag time and finishes earlier too. Thus, these patients are ready for intubation after a longer time. Moreover, we have to repeat cisatracurium injections after shorter intervals to maintain the desired level of blockade.

Health-Related Quality of Life of Breast Cancer Patients in iran: Pooled Analysis using Generalized Estimating Equations

The aim of current study was to evaluate the changes of health-related quality of life (HRQoL) and its clinical, demographic and socioeconomic determinants during chemotherapy and 4 months follow-up in women with breast cancer using a repeated measures framework. A double blind cohort study was performed in 100 breast cancer patients given fluorouracil, doxorubicin and cyclophosphamide (FAC) or docetaxel, doxorubicin, cyclophosphamide (TAC) in south of Iran. HRQoL was assessed at baseline, end of chemotherapy and four months thereafter using the QLQ-C30 questionnaire from European Organization for Research and Treatment of Cancer (EORTC). Generalized estimating equations (GEE) was applied for statistical analysis. The mean of age at baseline was 48.5±10.6. 70% and 14% of patients were married and smokers, respectively, and 20% suffered from another disease besides breast cancer. The results of GEE showed that after control for baseline scores, the HRQoL significantly improved over time. Although, the patients in FAC group had higher scores than the TAC group, the differences also diminished over time. Smoking, marital status and having child affected some scales of HRQoL. None of other variables were significantly related to HRQoL. Although patients in TAC groups had lower level of HRQoL over 8 months follow up, they experienced faster improvement than the FAC group. This implies that in long-term, improvements in TAC group are higher than FAC. Having children was positively correlated with HRQoL. Generally, there were no demographic and socio-economic differences in HRQoL in these patients between the chemotherapeutic regimens.

Genotype Frequencies of Selected Drug Metabolizing Enzymes and ABC Drug Transporters among Breast Cancer Patients on FAC Chemotherapy

Polymorphic genes of drug metabolizing enzymes and transporters may influence drug response. With some exemptions, single nucleotide polymorphisms in such genes, however, are not known to be susceptibility factors for breast cancer. This study explored genotype profiles for the breast cancer patients on fluorouracil, doxorubicin and cyclophosphamide (FAC) in a Pakistani set of population and their comparison with HapMap data. Sixty-eight female breast cancer patients were included. All received FAC chemotherapy. Relevant genotyping was done either through restriction fragment length polymorphism or pyrosequencing. The variant allele frequencies were: 5.1% for CYP2C9*2 (430C>T), 15.4% for CYP2C9*3 (1075A>C), 27.2% for CYP2C19*2 (681G>A), 33.1% for GSTA1*B (-69C>T, -52G>A), 62.5% for ALDH3A1*2 (985C>G), 58.8% and 4.4% for ABCB1 (2677 G>T/A), 64.7% for ABCB1 3435 C>T, and 15.4%, 33.1% and 39.7% for ABCC2 (-24 C>T, 1249 G>A and 3972 C>T). In comparison with HapMap, this first exploration in Pakistani samples shows higher frequency of (i) CYP2C9*3 carriers (p < 0.05) than in Hispanic, Chinese, Japanese and African samples, (ii) ALDH3A1*2 carriers (p < 0.01) than Caucasian, Hispanic, Chinese, Japanese and African samples. For ABC transporters, a higher frequency of variant allele was observed in (iii) ABCB1 2677 G>T/A (p < 0.01) than Caucasian, Hispanic and African, (iv) ABCB1 3435 C>T (p < 0.05) than Chinese, Japanese and African, (v) ABCC2 1249 G>A (p < 0.01) than Hispanic, Chinese and Japanese samples. In conclusion, cyclophosphamide activation and detoxification of reactive intermediates may be altered in the Pakistani. Though carriers of CYP2C19*2 were higher than in Caucasian and Hispanics, they did not reach statistical significance (p = 0.05).

Cost–effectiveness analysis of adjuvant therapy for node positive breast cancer in Korea: docetaxel, doxorubicin and cyclophosphamide (TAC) versus fluorouracil, doxorubicin and cyclophosphamide (FAC)

This study evaluated the incremental cost-effectiveness (ICER) and cost-utility ratios (ICUR) of TAC compared with FAC following primary surgery for node positive breast cancer patients in Korea. A cost-effectiveness analysis was performed using the Markov model from the combined view of Korean National Health Insurance and patients. The model allowed assessment from the beginning of the first cycle of adjuvant chemotherapy following primary surgery until death. Relevant clinical data were obtained from the clinical trial BCIRG 001 and data for local treatment patterns and direct medical costs were obtained from three Korean hospitals. Over a life time horizon, the life expectancy of TAC was 0.9 years longer than that of FAC. The ICER was 8,025,879 Korean won (KW, 6,573 euro) per life year gained and the ICUR was 8,885,794 KW (7,277 euro) per QALY gained when the cost and effectiveness were discounted at 5%. The model was most sensitive to the percent patient receiving prophylactic granulocyte colony stimulating factor (G-CSF) in TAC arm and the ICUR was 12,119,561 KW (9,926 euro) when assuming 100%. TAC appears to be cost-effective in the management of early breast cancer in Korea.

Docetaxel in Combination With Doxorubicin and Cyclophosphamide As Adjuvant Treatment for Early Node-Positive Breast Cancer: A Cost-Effectiveness and Cost-Utility Analysis

To estimate the cost effectiveness of TAC (docetaxel, doxorubicin, and cyclophosphamide) compared with FAC (fluorouracil, doxorubicin, and cyclophosphamide) when administered as adjuvant therapy to women with node-positive early breast cancer in the United Kingdom (UK), both with and without primary prophylaxis with granulocyte colony-stimulating factor (G-CSF). A standard health economic Markov model estimated the cost and outcome for node-positive early breast cancer patients, from initiation of adjuvant chemotherapy to death. Patient-level data were used from the Breast Cancer International Research Group (BCIRG) 001 trial for estimates of the effect of chemotherapy on toxicity and outcome, and an observational data set collected from a UK university hospital provided estimates of resource use and outcome for patients with relapsed disease. Over a 10-year analysis timeframe, the incremental cost per life-year saved associated with the use of TAC rather than FAC was estimated as pound 15,418 (95% CI, pound 13,734 to pound 17,997) and the incremental cost per quality-adjusted life-year gained (IC/QALY) was pound 18,188 (95% CI, pound 14,161 to pound 32,422). The addition of primary G-CSF (lenograstim or filgrastim) to the TAC regimen resulted in an IC/QALY of pound 20,432. The results were most sensitive to the quality-of-life (QOL) score for patients in remission postchemotherapy. However, even if QOL was assumed to be as poor as for patients with metastatic disease, the IC/QALY estimate rose only to pound 32,430. The use of adjuvant TAC rather than FAC for node-positive early breast cancer patients is cost effective, despite the increased drug and toxicity treatment costs, and when primary G-CSF prophylaxis is given to all patients.

A new measurement of residual cancer burden to predict survival after neoadjuvant chemotherapy

536 Background: The strength of association between tumor response and survival is critical for neoadjuvant chemotherapy trials. Pathologic complete response (pCR) reliably predicts survival benefit, but residual disease contains a range of pathologic responses that likely contain different prognostic groups, including near complete response and resistance. Methods: Pathologic slides and reports were reviewed from 432 patients in two completed neoadjuvant trials: 1) fluorouracil, doxorubicin and cyclophosphamide (FAC) in 189 patients, and 2) paclitaxel followed by FAC (T/FAC) in 243 patients. Paclitaxel was administered as twelve weekly (n=126) or four 3-weekly cycles (n=117). Residual cancer burden (RCB) was calculated as an index that combines pathologic measurements of primary tumor (size and cellularity) and nodal metastases (number and size). We compared four RCB categories, from RCB-0 (pCR) to RCB-3 (chemoresistant), and post-treatment revised AJCC Stage (0-III) for prediction of distant relapse-free survival (DRFS) in multivariate Cox regression analyses (stratified by ER status). Results: The pCR rate was greater after T/FAC than FAC (24% vs. 16%, LR p&lt;0.05), and after weekly (vs. 3-weekly) paclitaxel in T/FAC (30% vs. 16%, LR p&lt;0.01). In patients with residual disease, RCB measurements were significantly lower after T/FAC than FAC (t-test, p&lt;0.0001), but were not different between paclitaxel schedules in T/FAC. RCB was a continuous predictor of DRFS after T/FAC (HR=1.86, 95%CI 1.51–2.30) or FAC (HR=1.67, CI 1.38–2.01) with median follow-up 5 and 8 years, respectively. The resistant category RCB-3 predicted relapse more strongly than AJCC Stage III and identified a larger group of high-risk patients ( Table ). Conclusions: RCB is a new continuous measure of pathologic response that is defined from routine pathologic materials, represents the distribution of residual disease, is a significant predictor of DRFS, and defines chemotherapy resistance more effectively than revised AJCC Stage. [Table: see text] [Table: see text]

Goserelin (‘Zoladex’)—offering patients more choice in early breast cancer

The luteinising hormone-releasing hormone analogue goserelin ('Zoladex') suppresses ovarian oestrogen production in pre- and perimenopausal women. Goserelin is a biodegradable, sustained-release 3.6 mg depot that is administered by subcutaneous injection every 28 days. Clinical trials in premenopausal women with hormone-sensitive early breast cancer have demonstrated that goserelin alone, or in combination with tamoxifen, is at least as effective as cyclophosphamide, methotrexate, 5-fluorouracil (CMF) chemotherapy. Goserelin plus tamoxifen after cyclophosphamide, doxorubicin and 5-fluorouracil (CAF) chemotherapy resulted in improved disease-free survival compared with CAF alone. These trials have also shown that goserelin is well tolerated and is associated with less acute toxicity than cytotoxic chemotherapy. Early improvements in quality of life over the first 3-6 months of goserelin treatment support the use of this agent as an alternative to chemotherapy in this patient population. Patients should be provided with information on the benefits and risks associated with available treatment options so that they can be involved in the decision-making process.

E2F1 expression is related with the poor survival of lymph node-positive breast cancer patients treated with fluorouracil, doxorubicin and cyclophosphamide.

The expressions of E2F1 and retinoblastoma protein (pRB) were analyzed in 165 lymph node-positive breast cancers. All patients underwent adjuvant chemotherapy with fluorouracil, doxorubicin and cyclophosphamide (FAC). E2F1 was expressed in 43.6% and pRB was expressed in 46.1%. E2F1 expression was significantly increased in pRB-expressing tumors and was associated with an S-phase fraction. By univariate survival analyses, E2F1 expression and ER were identified as significant prognostic factors for disease recurrence and patient survival. E2F1 was the only significant prognostic factor of patient outcome after FAC chemotherapy by multivariate analysis.

Adjuvant chemo-hormonal therapy with cyclophosphamide, doxorubicin and 5-fluorouracil (CAF) with or without medroxyprogesterone acetate (MPA) for node-positive cancer patients, update at 12 years follow up

An update with 10 years of follow up of a study adding adjuvant MPA to CAF chemotherapy is presented. A total of 409 patients were entered, of which 200 were randomized to receive 500 mg of MPA i.m. on days 1–28 and twice per week thereafter for 6 months. There was a significant improvement in metastases-free and overall survival in women >60 years of age receiving MPA (P=0.01 and P=0.02 respectively). A detrimental effect of MPA was seen in women <40 years. Possible reasons for these results are discussed.

High Efficacy of a Single Oral Dose of Ondansetron 8 mg Versus a Metoclopramide Regimen in the Prevention of Acute Emesis Induced by Fluorouracil, Doxorubicin and Cyclophosphamide (FAC) Chemotherapy for Breast Cancer

The aim of our single-center, prospective, randomized, open study was to evaluate the antiemetic efficacy and tolerability of a regimen based on a single oral dose of ondansetron 8 mg in comparison with a metoclopramide-based regimen, for prevention of acute FAC (fluorouracil, doxorubicin and cyclophosphamide) chemotherapy-induced emesis. A total of 149 chemotherapy-naive, female outpatients, under 50 years of age and with no history of alcohol consumption, scheduled to receive their first cycle of FAC chemotherapy, were included. The patients received either oral ondansetron (8 mg) or metoclopramide (1.5 mg/kg, i.v.), both combined with dexamethasone (16 mg, i.v.) and alprazolam (0.5 mg t.i.d. orally). No antiemetic prophylaxis was given for delayed emesis. Complete control of acute vomiting was obtained in 69/74 (93%) of patients receiving ondansetron, and in 49/75 (65%) of those receiving metoclopramide (p=0.00003). Complete control of acute nausea was obtained in 58% of patients receiving ondansetron and in 36% of those receiving metoclopramide (p=0.007). Complete prevention of delayed vomiting/nausea was achieved in 73%/20% and 60%/16% of patients, respectively. Sedation was more frequent in the metoclopramide arm (p=0.04). As far as we know this is the first study that supports the efficacy of a regimen based on a single oral dose of ondansetron 8 mg in the prevention of acute FAC chemotherapy-induced emesis. The ondansetron regimen was highly effective in female patients and was superior to the metoclopramide based regimen.

Adjuvant chemohormonal therapy with cyclophosphamide, doxorubicin and 5-fluorouracil (CAF) with or without medroxyprogesterone acetate for node-positive breast cancer patients

The Comprehensive Cancer Center trial 82-01 is a prospective randomized study to investigate the value of the addition of high-dose medroxyprogesterone acetate (MPA) to chemotherapy in patients with node-positive operable breast cancer. MPA may be of advantage in this setting because of its activity in estrogen receptor ER-positive as well as ER-negative tumors and since it may protect against chemotherapy-induced myelosuppression and thus enable maintenance of the appropriate chemotherapeutic scheduling. Four hundred eight evaluable patients with node-positive (N+) operable breast cancer (T1-3, N1) were entered in a multicenter randomized trial. Two hundred nine patients were randomized in the MPA- arm and 199 in the MPA+ arm. CAF chemotherapy was given as a short i.v. bolus infusion: cyclophosphamide 500 mg/m2 i.v. day 1, doxorubicin 40 mg/m2 i.v. day 1, and 5-fluorouracil 500 mg/m2 i.v. day 1, q 4 wks x 6. MPA was given intramuscularly (i.m.) 500 mg q d x 28 days, followed by 500 mg i.m. twice weekly during 5 months. The main side effects of MPA were weight gain with a mean of 5.5 kg as opposed to 1.8 kg in the control group (p = 0.01) and vaginal bleeding in 30/199 in the MPA+ group and 0 in the MPA- group. MPA ameliorated vomiting grade III, IV (45% vs. 28%, p < 0.001), nausea grade III, IV (50% vs. 34%, p < 0.001) and leucocyte nadir grade III, IV (20% vs. 11%, p = 0.003). Disease-free survival (DFS) after 5 years was 59% in the MPA+ and 49% in the MPA- group (p = 0.12). Patients > or = 60 years benefitted most from MPA treatment, in particular if freedom from distant metastases was taken as the endpoint (p = 0.02). Overall survival (OS) was not significantly different between the two treatment groups (p = 0.18), but within subgroups analysed there was an advantage for MPA+ in patients > or = 55 years (p = 0.002) and in pT1 patients (p = 0.045). High-dose MPA ameliorates CAF side effects and reduces the risk of metastatic disease, especially in elderly breast cancer patients.

Neoadjuvant chemotherapy with cyclophosphamide, doxorubicin and 5-fluorouracil (CAF) or cyclophosphamide, methotrexate and 5-fluorouracil (CMF) in 69 cases of locally advanced (stage IIIb) breast cancer

Sixty nine patients with a median age of 45 years, 62.3 per cent of whom were premenopausal, with locally advanced breast cancer (T 4, N 0-3, M 0; Stage IIIb) were treated with 3 cycles of either neoadjuvant cyclophosphamide, doxorubicin and 5-fluorouracil, being the CAF group: 36 patients, or cyclophosphamide, methotrexate and 5-fluorouracil, being the CMF group: 33 patients. Patients achieving complete response or with residual disease of less than 2 cm in diameter received radical radiotherapy while those with more residual disease underwent radical mastectomy. Nine cycles of adjuvant chemotherapy were administered. Complete responses and disease control by radiotherapy with complete breast preservation were more frequently observed after CAF than CMF, being 25 per cent vs 3 per cent (p = 0.025) and 48.5 per cent vs 12 per cent (p = 0.002), respectively. Overall response rates, adverse effects, disease control following radiotherapy/surgery, local relapses and metastases were similar for both regimes. Relapsing patients were young, with a median age of 38 years, 68.4 per cent of relapses occurred at metastatic sites and 42 per cent of relapses occurred during adjuvant chemotherapy. This study suggests that in locally advanced breast cancer, a greater proportion of patients can be rendered disease free after neoadjuvant CAF and radiotherapy compared to neoadjuvant CMF and radiotherapy.

Effect of chemotherapy with or without buserelin on serum hormone levels in premenopausal women with breast cancer

Serial determinations of serum oestradiol (E2), follicle-stimulating hormone (FSH) and luteinising hormone (LH) were done to assess the effect of chemotherapy, with or without a gonadotropin-releasing hormone analogue, buserelin, on ovarian function in 147 premenopausal women treated for breast cancer. Cyclophosphamide, doxorubicin and 5-fluorouracil (CAF) plus buserelin was given to 81 women with metastatic disease, and 66 women were randomised to adjuvant cyclophosphamide, methotrexate and 5-fluorouracil (CMF) with buserelin or CMF alone. Baseline mean E2 of patients treated with cytostatics plus buserelin fell from premenopausal levels and remained low while patients were on study. E2 levels remained at premenopausal values in patients treated with CMF alone. Downregulation of FSH and LH occurred with cytostatics plus depot buserelin, but fluctuated with the nasal administration; on CMF alone, FSH and LH levels increased. Buserelin plus cytostatics more effectively caused ovarian ablation than cytostatic treatment alone. Depot buserelin was more effective than nasal buserelin.

Long-term survival of patients treated with combination chemotherapy for metastatic breast cancer

Long-term survival of patients with metastatic breast cancer treated on two prospective stratified randomised trials has been analysed. Patients on study B122 received either cyclophosphamide, methotrexate and 5-fluorouracil (CMF) or cyclophosphamide, doxorubicin and 5-fluorouracil (CAF). On study B141 patients received CAF or mitolactol (dibromodulcitol), doxorubicin and vincristine alternating after every three cycles with three cycles of CMF (DAV/CMF). Long-term follow-up of 172 patients showed no significant survival difference (in multivariate regression models) for treatment with either CMF vs. CAF vs. DAV/CMF. The difference in median survival times between CMF and CAF showed a trend in favour of CAF. Advances in the management of metastatic breast cancer in postmenopausal women obtained by doxorubicin regimens have had a small but measurable impact on survival, but known patient discriminants were not overridden by the treatment regimens investigated in these studies.

The Antiemetic Efficacy of Thiethylperazine and Methylprednisolone Versus Thiethylperazine and Placebo in Breast Cancer Patients Treated with Adjuvant Chemotherapy (Fluorouracil, Doxorubicin and Cyclophosphamide): A randomized, double-blind, cross-over trial

Forty-six women with breast cancer treated with adjuvant FAC (fluorouracil, doxorubicin and cyclophosphamide) entered a multicenter, randomized, double-blind, cross-over trial in which thiethylperazine (T) (6.5 mg p.o every 8 h x 3 days) plus methylprednisolone (MP) (250 mg i.v. x 2 doses) was compared with thiethylperazine plus placebo. Forty-four patients were evaluable for efficacy. T + MP was significantly better in reducing vomiting (p less than 0.01) and nausea (p less than 0.02). The complete protection rate against vomiting was 36% for T + MP compared to 18% for T + placebo, and the percentage of nausea grades 0 + 1 (none or slight) was 59% and 27% respectively. The patient preference after cross-over was strikingly in favor of T + MP (70% versus 13%) (p less than 0.001). The most important side-effects of T + MP were facial flushing (22%) and euphoria (27%). Other side-effects, such as dryness of the mouth and sedation, were common after both treatments. In conclusion, the study suggested that T + MP is superior to T alone in protecting from nausea and vomiting induced by FAC.