[Epirubicina neoadyuvante con o sin docetaxel secuencial en el tratamiento del cáncer de mama avanzado: evaluación de la respuesta patológica completa y tolerabilidad de la quimioterapia]. / Neoadjuvant epirubicin with or without sequential docetaxel in treatment of advanced breast cancer: assessment of pathological complete response and chemotherapy tolerability.

OBJECTIVE: To assess the pathological complete response (pCR) rate after neoadjuvant chemotherapy (NC) with anthracyclines with or without taxanes in management of locally advanced breast cancer (LABC). METHOD: Patients with LABC were included. A cohort received four cycles of 5-fluorouracil [FEC] (FEC 500 mg/m2, epirubicin 75 mg/m2, cyclophosphamide 500 mg/m2) every 3 weeks followed by four cycles of docetaxel (D) 75 mg/m2 as 1 h infusion intravenous every 3 weeks. Another cohort received six cycles of FE100C (500, 100 and 600 mg/m2). The chemotherapy was followed by surgery and radiotherapy. RESULTS: There was no statistically significant difference in overall response rate (ORR) (ORR: 78.5 vs. 85%; p = 0.299) and clinical complete response (cCR) (c CR: 20.6 vs. 33.3%; p = 0.103) for 4FEC→4D compared to 6FE100C, respectively. Instead, there was a statistically significant improved rate of pCR (30.2 vs. 16.7%; p = 0.049) and negative axillary lymph nodes (51.6 vs. 35%; p = 0.03) for 4FEC→4D compared to 6FE100C, respectively. Serious toxicity was low and non-significant in both cohorts. The logistic regression multivariate models showed that main significant predictors to obtain a pCR were 4FEC→4D NC (odds ratio [OR]: 2.7; p = 0.019) and stage IIIA (OR: 3.8; p = 0.002). CONCLUSION: This study showed that 4FEC→4D regimen with conventional dose is highly active and well tolerated in patients with LABC in our hospital.

OBJETIVO: Evaluar la tasa de respuesta patológica completa (RPc) posterior a la quimioterapia neoadyuvante (QN) con antraciclinas con o sin taxanos en el manejo del cáncer de mama localmente avanzado (CMLA). MÉTODO: Se incluyeron pacientes con CMLA. Una cohorte recibió cuatro ciclos de FEC (5-fluorouracilo 500 mg/m2, epirubicina 75 mg/m2, ciclofosfamida 500 mg/m2) cada 3 semanas seguido por cuatro ciclos de docetaxel (D) 75 mg/m2 en infusión intravenosa de 1 hora cada 3 semanas. Otra cohorte recibió seis ciclos de FE100C (500, 100 y 600 mg/m2). Se realizó cirugía posterior a la quimioterapia. RESULTADOS: No hubo diferencia estadísticamente significativa en las tasas de respuesta objetiva (78.5 vs. 85.0%; p = 0.299) ni en la respuesta clínica completa (20.6 vs. 33.3%; p = 0.103) para 4FEC→4D comparado con 6FE100C, respectivamente. En cambio, hubo una mejora significativa en la tasa de RPc (30.2 vs. 16.7%; p = 0.049) y en los ganglios linfáticos axilares negativos (51.6 vs. 35%; p = 0.03) para 4FEC→4D en comparación con 6FE100C, respectivamente. La toxicidad grave fue baja y no significativa en ambas cohortes. Los modelos multivariados de regresión logística mostraron que los principales predictores significativos para obtener una RPc fueron la QN con 4FEC→4D (odds ratio [OR]: 2.7; p = 0.019) y el estadio IIIA (OR: 3.8; p = 0.002). CONCLUSIÓN: Este estudio mostró que el régimen 4FEC→4D con dosis convencional es muy activo y bien tolerado en pacientes con CMLA en nuestro hospital.

Early assessment of the left ventricular function by epirubicin-induced cardiotoxicity in postoperative breast cancer patients.

OBJECTIVE: Epirubicin (Epi) is a potent and effective drug for many malignant cancers with serious cardiotoxicity. Therefore, layer-specific two-dimensional speckle tracking echocardiography (2D-STE) was used to evaluate the longitudinal and circumferential systolic function of the left ventricular for the early detection of cardiotoxicity in this retrospective work. METHODS: Overall, 130 female patients with postoperative breast cancer who did not receive radiotherapy were classified into three groups: Group A (control group, n = 40) without any chemotherapy; Group B (n = 44) administered Epi at 180 ~ 240 mg/m2 ; and Group C (n = 46) administered Epi at ≥360 mg/m2 . Peak and global systolic longitudinal strains (GLS) in the total and endocardium, mid-myocardium, and epicardium were measured and calculated from apical four-chamber, apical two-chamber, and left ventricular long-axis views, respectively. Peak and global circumferential strains (GCS) in the total and endocardium, mid-myocardium, and epicardium were measured and calculated from mitral annulus, papillary muscle, and apical levels of the short-axis view, respectively. RESULTS: The total GLS and GLS of the endocardium in every view were significantly reduced in group C compared with both groups A and B (P < .05), but there was no significant difference between groups A and B (P > .05). The GLS of the epicardium and mid-myocardium in groups B and C were not significantly reduced (P > .05). There were no significant differences in the total GCS and layer-specific GCS of endocardium, mid-myocardium, and epicardium among the three groups (P > .05). CONCLUSIONS: Left ventricular longitudinal systolic dysfunction was detected. Moreover, an impaired endocardium was also detected in an early assessment by layer-specific 2DSTE.

Cardiac assessment of early breast cancer patients 18 years after treatment with cyclophosphamide-, methotrexate-, fluorouracil- or epirubicin-based chemotherapy.

BACKGROUND: Epirubicin-based chemotherapy improves the outcome of early breast cancer (BC) patients. However, cardiotoxicity remains an important side effect. METHODS: We re-consented node-positive BC patients enrolled in a phase III trial between 1988 and 1996 which compared six cycles of oral cyclophosphamide, methotrexate, fluorouracil (CMF) versus two epirubicin-cyclophosphamide regimens differing by the anthracycline cumulative dose [standard-dose epirubicin and cyclophosphamide (SDE) (8 × 60 mg/m(2)) and higher-dose epirubicin and cyclophosphamide (HDE) (8 × 100 mg/m(2))]. Eligible patients were those who were alive and free of disease and had no contra-indications to the proposed tests (cardiac evaluation). Cardiotoxicity was defined as asymptomatic systolic dysfunction (left ventricular ejection fraction (LVEF)< 50%, New York Heart Association (NYHA) Class I) or symptomatic heart failure (NYHA Class II-IV). Differences in cardiotoxicity between CMF and SDE/HDE were assessed using chi-square and Fisher Exact tests for binary variables and t-test and Wilcoxon test for continuous variables. RESULTS: Among the 777 patients, 20 cases of CHF were reported (CMF = 1, SDE = 5, HDE = 14; p < 0.001). Between September 2010 and June 2013, 82 patients (30%) out of 269 eligible patients accepted to participate in this substudy. Median follow-up was 18 years (range 15-24). Epirubicin-treated patients had significantly higher heart rate, more abnormal echocardiograms and LVEF by magnetic resonance imaging (MRI) compared to CMF-treated ones. A trend towards higher BNP was also observed in the SDE/HDE group (P = 0.08). No differences were observed in LVEF assessed by echocardiogram or troponin T levels. CONCLUSIONS: Participation rate in this substudy was lower than expected highlighting the complexity of re-calling patients several years after the initial BC diagnosis. After 18 years, epirubicin-treated patients had a lower LVEF by MRI, more abnormal echocardiograms, higher heart rates compared to patients treated with CMF. However, no major delayed cardiotoxicity was observed.

[Velocity vector imaging assessment of early epirubicin-induced myocardial damage].

OBJECTIVE: To assess the left ventricular (LV) longitudinal systolic and diastolic function in patients treated by epirubicin by velocity vector imaging (VVI) and to discuss the important clinical value of VVI in quantitatively evaluating the regional longitudinal function. METHODS: Thirty patients with breast cancer treated with epirubicin chemotherapy and 30 normal controls were included in the study. Dynamic images of apical long axis, four-chamber and two chamber view were obtained in all subjects, and the longitudinal systolic and diatolic parameters were measured in all subjects, including systolic maximum velocity (Vs), systolic maximum strain (SS), systolic maximum strain rate (SSR), diastolic maximum velocity (Vd), and diastolic maximum strain rate (DSR). The parameters were compared between the 2 groups. The conventional echcardiographic parameters were also obtained. RESULTS: There was no significant change in all baseline parameters before the chemotherapy in 30 breast cancer patients compared with the normal controls (P>0.05). After the second chemotherapy cycle, DSR was lower in every segment, Vd was lower in the free wall, mainly the lateral, anterior and inferior wall (P<0.05), while Vd didn't change significantly in the septum wall (P>0.05). After the third chemotherapy cycle, Vd, DSR and SSR decreased significantly in all segments (P<0.05). Vs and SS didn't change significantly (P>0.05). CONCLUSION: VVI can monitor the epirubicin cardiotoxicity early and is more sensitive than echocardiograph.

[Assessment of nausea and vomiting during FEC regimen for breast cancer after the novel antiemetic agent - introduction using MASCC antiemesis tool].

Chemotherapy-induced nausea and vomiting(CINV)is one of the side effects causing significant psychological and physical suffering in patients receiving chemotherapy. Because CINV often impairs patients' quality of life and leads to discontinuation of treatments, antiemetic therapy has been considered important. The MASCC Antiemesis Tool(MAT)was proposed for the assessment of acute and delayed nausea and vomiting after, we evaluated the actual situation of nausea and vomiting for Japanese patients. In a previous investigation, even conventional antiemesis therapy was a highly effective treatment during the acute phase, but the control of nausea and vomiting during the delayed phase proved difficult. Recently, a new5 -HT3 receptor blocker(palonosetron)and an NK1 receptor blocker(aprepitant) were introduced, and an effective treatment of nausea and vomiting for the delayed phase is non expected. In this examination, we evaluated the usefulness of the new antiemetic drugs(palonosetron and aprepitant)in 12 prospective patients with breast cancer(40-69 years old, median age 53 years old)for whom FEC therapy was given as an ambulant treatment using MAT. No vomiting occurred in the acute and delayed phase. Nausea during the acute phase was controlled, and was mild during the delayed phase, also. It was confirmed that the onset of acute and delayed nausea and vomiting were relieved by the newantiemetic agents compared with the previous MAT evaluation.

Tissue-Doppler assessment of cardiac left ventricular function during short-term adjuvant epirubicin therapy for breast cancer.

BACKGROUND: It has been hypothesized that the extent of acute anthracycline-induced cardiotoxicity reflects the risk for late development of heart failure. The aim of this study was to examine if short-term changes in cardiac function can be detected even after low-dose adjuvant epirubicin therapy for breast cancer when using Doppler tissue imaging of longitudinal left ventricular function. METHODS: Eighty consecutive women in good cardiopulmonary health scheduled to undergo adjuvant treatment for breast cancer were included. They were examined using echocardiography and Doppler tissue imaging before and after three treatment series of epirubicin (mean cumulative dose, 273.7 ± 46.6 mg/m(2); median time interval, 9 weeks; range, 47-113 days). RESULTS: Apart from a marginal reduction in E/A ratio, none of the conventional Doppler echocardiographic or Doppler tissue imaging indices of systolic and diastolic function were affected during epirubicin treatment. CONCLUSIONS: In contrast to several previous studies using tissue Doppler and conventional echocardiography, this study did not document relevant short-term effects of low-dose epirubicin treatment on heart function.

Good clinical and cost outcomes using dexrazoxane to treat accidental epirubicin extravasation.

A 75-year-old man diagnosed with lower esophageal adenocarcinoma suffered from epirubicin extravasation during the second cycle of neoadjuvant chemotherapy with epirubicin and oxaliplatin. A full recovery was achieved after treatment with dexrazoxane (Cardioxane® ). This is the first time in our hospital that extravasation of an anthracycline has been treated with dexrazoxane. We used Cardioxane® , approved for the prevention of anthracycline-induced cardiotoxicity, while Savene® is indicated for the treatment of anthracycline extravasation. The treatment was effective, and the selection of Cardioxane® (seven-fold cheaper than Savene® ) yielded a cost saving. Consequently, Cardioxane® has been included in our guidelines for anthracycline extravasation.

Quality of life assessment in advanced pancreatic adenocarcinoma: results from a phase III randomized trial.

BACKGROUND: A phase III trial suggested that a PEFG (cisplatin, epirubicin, 5-fluorouracil, gemcitabine) regimen might improve the outcome compared to gemcitabine in advanced pancreatic adenocarcinoma. The analysis of treatment impact on quality of life (QOL) is reported. METHOD: Patients completed the European Organization for Research and Treatment of Cancer QLQ-C30 and PAN-26 questionnaires at baseline and every second month of treatment until disease progression. RESULTS: The largest differences between arms favored PEFG. Expressed as improvement > or =10 points from baseline (PEFG/gemcitabine), these were: emotional function (43/18%), fatigue (41/17%), QOL (55/29%), pain (64/41%), and flatulence (50/26%). Only change in sexual function favored gemcitabine (19/42%). Physical function, fatigue, appetite, and satisfaction with healthcare improved in 40-46% of partial responders compared with 0-12% of patients with stable disease. CONCLUSION: Clinically relevant improvement in QOL from baseline was observed more often after PEFG than after gemcitabine, suggesting that the PEFG regimen did not impair QOL, Partial response was associated with improved QOL suggesting that effective treatment of pancreatic adenocarcinoma may have an important role in these patients.

Clinical and economic impact of epoetin in adjuvant-chemotherapy for breast cancer.

INTRODUCTION: Anaemia is a common toxicity in cancer patients and epoetins (EPOs) are now an established treatment. The economic profile of EPO treatment was assessed in patients with breast cancer treated by adjuvant-chemotherapy. MATERIALS AND METHODS: Two strategies were compared: without treatment by EPO and with the possible use of treatment by EPO (epoetin alfa) when required. The clinical effectiveness criterion was time adjusted to quality of life and economic data included only direct medical costs. MAIN RESULTS: One hundred ninety-two patients were included. In the group with the strategy containing the possible use of EPO, 45.5% of patients effectively received EPO. A significant difference in the haemoglobin level profile over time was observed which provided a significant overall benefit of 0.0052 (p<10(-4)) quality-adjusted life year (QALY) associated with an extra cost of 1,615 (p<10(-4)). In the base case analysis, the cost per added QALY was estimated as 310,577 with the strategy containing the possible use of EPO. CONCLUSION: This robust result seems to be unacceptable, but the only relevant point of discussion might be the level of acceptable incremental cost-effectiveness ratio (ICER) for a patient.

Prospective randomized phase III trial of etoposide/cisplatin versus high-dose epirubicin/cisplatin in small-cell lung cancer.

High-dose epirubicin plus cisplatin was compared with the reference regimen of etoposide/cisplatin in small-cell lung cancer (SCLC). Four hundred two previously untreated patients with SCLC were randomized to receive etoposide 100 mg/m(2) on days 1-3 and cisplatin 100 mg/m(2) on day 1 or epirubicin 100 mg/m(2) and cisplatin 100 mg/m(2) on day 1 every 21 days for a total of 6 cycles. Patients were stratified according to treatment center and extent of disease (limited disease, n = 207; extensive disease, n = 195). Patients with limited disease were treated with thoracic radiation therapy after completion of chemotherapy, and those who exhibited a complete response were advised to receive prophylactic cranial irradiation. The primary endpoint was survival, and secondary endpoints were time to progression (TTP), response, toxicity, and costs. Patient characteristics were generally well balanced in the 2 arms, even though more patients in the epirubicin/cisplatin arm had > 5% weight loss and poor Karnofsky performance index compared with the etoposide/cisplatin arm. One hundred thirty-four patients (66.3%) in the etoposide/cisplatin arm and 126 (63.0%) in the epirubicin/cisplatin arm received all 6 planned cycles of chemotherapy. Response rate, TTP, and survival did not differ significantly between the 2 arms. Grade 3/4 neutropenia and toxic deaths occurred more frequently in the etoposide/cisplatin arm. Epirubicin/cisplatin showed a similar activity with a slightly lower toxicity profile than the reference regimen of etoposide/cisplatin. The epirubicin/cisplatin regimen may be recommended in the treatment of SCLC.

Doxorubicin liposomal pegylated: new preparation. Breast cancer: not just a question of short-term cardiac effects.

(1) There is no reference first-line chemotherapy regimen for metastatic breast cancer. Anthracycline-based combinations are generally used. One of the main problems with anthracyclines is the risk of heart failure, both during and some time after treatment. (2) A liposomal pegylated doxorubicin, an anthracycline, is now available in Europe. The aim of pegylation is supposedly to reduce the cardiotoxicity relative to standard doxorubicin. The marketing licence specifies that liposomal pegylated doxorubicin must not be used in combination with other drugs in people with metastatic breast cancer. This is the second liposomal doxorubicin preparation to be authorised for this use in France; we concluded that the first product, a non-pegylated form, offered no therapeutic advance. (3) According to the only available comparative trial, liposomal pegylated doxorubicin is no more effective than standard doxorubicin in terms of the duration or quality of survival. (4) In this trial, liposomal pegylated doxorubicin was associated with slightly fewer cardioechographic abnormalities than standard doxorubicin. (5) Other adverse events were also less common (hair loss, nausea and vomiting, and neutropenia), while some were more common (palmoplantar erythrodysesthesia, stomatitis and mucitis). Overall, 24% of patients stopped using liposomal pegylated doxorubicin because of adverse events, compared with 11% of patients receiving standard doxorubicin. (6) Unlike liposomal non-pegylated doxorubicin, the liposomal pegylated form is no more difficult than standard doxorubicin to prepare for injection. (7) In practice, when the decision is made to use doxorubicin, the standard form, at an appropriate dose, is suitable for most patients, as long as cardiac function is closely monitored. Differences in the adverse effect profile (especially hair loss) may make liposomal pegylated doxorubicin more attractive to some patients (it costs 20 times more than standard doxorubicin in France).

Liposomal doxorubicin in breast cancer: new preparation. Much ado about nothing.

(1) There is no reference first-line cytotoxic chemotherapy protocol for metastatic breast cancer, but anthracycline combinations are commonly used. In addition to their myelotoxicity, anthracyclines can cause heart failure, both problems during and after treatment. (2) A liposomal formulation of doxorubicin, an anthracycline, has been developed with the aim of reducing this cardiotoxicity. The marketing terms specify that it must be used in combination with cyclophosphamide, in the first-line treatment of metastatic breast cancer. (3) According to the current evaluation file, which chiefly includes data from three comparative trials, liposomal doxorubicin is no more effective, in terms of the duration or quality of survival, than standard doxorubicin or epirubicin. (4) During comparative trials of liposomal doxorubicin, alone or in combination with cyclophosphamide, signs of cardiotoxicity, as measured by ultrasound, were slightly less frequent than with standard doxorubicin but no less frequent than with epirubicin. Given the possibility of late cardiac events, which were not studied in these trials, there is no evidence that liposomal doxorubicin is really less cardiotoxic than either standard doxorubicin or epirubicin. As regards other adverse effects, liposomal doxorubicin has no advantages over standard doxorubicin or epirubicin. (5) Liposomal doxorubicin is far more difficult to prepare than standard doxorubicin. (6) In France, liposomal doxorubicin is about 15 times more expensive than standard doxorubicin and 4 times more expensive than epirubicin. (7) In practice, standard doxorubicin can still be used, at doses appropriate for the individual patient and with cardiac monitoring.

Neutropenic infections add significant costs to palliative chemotherapy in breast cancer.

BACKGROUND: The key clinical question in treating cancer patients for palliation is balancing issues on efficacy, toxicity and cost. The costs of chemotherapy have risen substantially during recent years, yet many patients are treated even at the end of their life with unresponsive cancer. The objective of this study was to determine the additional treatment costs during six months on chemotherapy to manage toxicity. PATIENTS AND METHODS: Thirty-eight women were treated for metastatic breast cancer with an epirubicin-docetaxel regimen every three weeks. The clinical benefit was calculated for responding and stable patients maintaining the same status for at least 6 months (% of evaluable patients). Data on the use of medical resources were extracted from the hospital records. Health resources utilization analyses included the costs in Euros at year 2000 values during the six months' treatment of all additional hospitalization, drugs and blood transfusions. RESULTS: The response rate (CRIPR) was 54% (95% CI 37-71). Seventy per cent of the patients (95% CI 53-84) had objective clinical benefit. The crude cost of the treatment was 12,416 Euros per patient. The total cost of chemotherapy per patient was 14,915 Euros. The costs of hospital stays, antibiotics, granulocyte growth factors and blood transfusions when indicated added 2,499 Euros per patient, thus adding 20% to crude treatment costs. CONCLUSION: The treatment of advanced breast cancer with 3-weekly epirubicin-docetaxel combination requires additional use of health resources mainly due to infections. The clinical benefit and true cost rates should be reported with the results of novel schedules.

Assessment of early epirubicin cardiotoxicity in women with breast cancer.

BACKGROUND: Anthracycline-containing chemotherapy has been the most frequently observed cause of iatrogenic cardiac damage in patients with breast cancer. The purpose of this study was to evaluate by radionuclide ventriculography whether a mean cumulative dose of epirubicin (MCDE) induced left ventricular (LV) systolic or/and diastolic dysfunction in 32 patients treated for breast cancer. MATERIALS AND METHODS: Thirty-two patients with breast cancer according to chemotherapeutical trials received MCDE of 360 m/m2. All patients were studied before and after they completed chemotherapy with radionuclide ventriculography at rest. Systolic and diastolic left ventricular parameters were assessed. RESULTS: Diastolic left ventricular parameters and R-R intervals significantly differed before and after completed chemotherapy in our patients: peak filling rate (PFR: 2.8 +/- 0.6 vs. 2.2 +/- 0.7 EDV/sec) and time to filling rate (TPFR: 182 +/- 48 vs. 2.25 +/- 50 msec), R-R: 723 +/- 51 vs. 620 +/- 45 msec, p < 0.01. Ejection fraction, as a systolic parameter/did not significantly differ before and after completed chemotherapy (EF: 59 +/- 7 vs. 58 +/- 6%), p > 0.05. CONCLUSION: Our results indicate that left ventricular diastolic dysfunction even at an MCDE of 360 mg/m2 may be an early sign of epirubicin cardiotoxicity.

Clinical relevance of radionuclide angiography and antimyosin immunoscintigraphy for risk assessment in epirubicin cardiotoxicity.

BACKGROUND: Cardiotoxicity is the major limiting factor in anthracycline chemotherapy of advanced neoplastic disease. Epirubicin shows a more favorable therapeutic index than does doxorubicin, but it is still cardiotoxic. Limited data regarding epirubicin cardiotoxicity are available, and suggested guidelines for doxorubicin with left ventricular ejection fraction (LVEF) measurement may not be empirically useful for epirubicin therapy. This study evaluates the diagnostic role of antimyosin immunoscintigraphy for early identification of patients at risk for late pump dysfunction from cardiotoxicity induced by high-dose administration of epirubicin up to high cumulative dosages. METHODS AND RESULTS: Chemotherapy with epirubicin was administered to 36 patients with cancer at a dosing rate of 160 mg/m2 as a bolus injection every 21 days to a cumulative dosage of 960 mg/m2. Radionuclide angiography (LVEF) and antimyosin immunoscintigraphy with heart-lung ratio (HLR) measurements were performed before chemotherapy, at intermediate cumulative epirubicin dosages, at the end of treatment, and during the follow-up. LVEF decreased significantly at the end of the treatment and after therapy discontinuation. HLR values were significantly increased at intermediate epirubicin dosage levels and continued to increase to the end of the treatment but thereafter remained substantially unmodified for 3 to 6 months after therapy discontinuation. A value of HLR >1.85 at intermediate epirubicin dosage level showed a sensitivity of 95% and a specificity of 57% as a predictor of late LVEF impairment. CONCLUSIONS: LVEF appears more useful at high cumulative dosages and during follow-up to monitor late pump dysfunction, whereas HLR may be effective during the early phase of the therapy in determining which patients are at risk for development of late cardiac dysfunction.

Prevention of delayed emesis by a single intravenous bolus dose of 5-HT3-receptor-antagonist in moderately emetogenic chemotherapy.

While the use of 5-HT3 receptor antagonists is clearly justified in patients receiving cisplatin, their role with less emetic drugs is still not defined. The aim of our randomized study was to verify the efficacy of the single standard dose of three 5-HT3-receptor-antagonists in moderately emetic chemotherapies. Sixty chemotherapy-naive breast cancer patients of 30 to 71 years in age, P.S. = 0-1, receiving 5-fluorouracil-epirubicin-cyclophosphamide (FEC 75) q 21 days or cyclophosphamide-methotrexate-5-fluorouracil (CMF) or 120 mg/m2 epirubicin or high dose mitomycin-methotrexate-mitoxantrone (MMM) q 14 days (+ G-CSF) or 100 mg/m2 epirubicin (+ G-CSF) were randomized to receive, 15 min before chemotherapy, 8 mg i.v. bolus of ondansetron or 3 mg i.v. granisetron or 5 mg i.v. tropisetron and no further antiemetic therapy in the following days. 180 cycles were evaluable. Complete protection, (the absence of vomiting episodes,) was respectively 75%, 70% and 70% in the acute and 70%, 82%, 72% in the delayed phases, and an absence of nausea was 56%, 37% and 20% in the acute phase and 50%, 35% and 27% in the delayed, respectively. Complete response, (absence of vomiting and absence or mild nausea,) was 74%, 58.6% and 50.8% in the acute and 64%, 63.7%, 47.3% in the delayed phases, respectively. At the statistical analysis no significant differences between the three drugs were found regarding acute vomiting while ondansetron was superior to granisetron and tropisetron in acute (p = 0.018; p < 0.05) and delayed nausea (P = 0.104; p < 0.01). This activity is practically the same as that we reported (Ann Oncol 1994; 6, suppl 8: 204) with a loading dose on day 1 and maintenance for the following 2-5 days, but with a significantly favorable cost-benefit ratio.

Economic analyses of toxicity secondary to anthracycline-based breast cancer chemotherapy.

Doxorubicin (D) is one of the most active agents in the treatment of breast cancer but can be associated with cardiotoxicity (CT) and febrile neutropenia (FN). Epirubicin, a stereoisomer of doxorubicin, is reported to have similar efficacy but reduced toxicity. A retrospective chart audit was performed to estimate the incidence, average length of hospitalisation and resource consumption for the management of CT and FN in 200 patients breast cancer patients receiving equidoses of doxorubicin or epirubicin. Overall, there were three more episodes of CT in the doxorubicin group than in epirubicin patients (five versus two) at a cost of Canadian dollars C$4268/episode. With regard to FN, there were 11 more episodes in the doxorubicin arm (25 versus 14) at a cost of C$5419/episode. The results of the study support the substitution of equidose epirubicin for doxorubicin in women undergoing treatment for malignancies of the breast. Such a policy may result in reduced toxicity-related management costs.