Pancreaticobronchial Fistula Diagnosed by MDCT.

Pancreatic duct disruption is a serious complication of acute or chronic pancreatitis. These ruptures may cause collections of pancreatic secretion leading to ascites but also to pleural or mediastinal effusions. Rupture into the bronchial tree, resulting in a pancreaticobronchial fistula, is also possible, but it is a rare complication. It should be considered if a patient with pancreatitis develops respiratory symptoms and requires cross-sectional imaging to identify pancreaticobronchial fistulae.

Bronchial lipoma : an unusual cause of pleural empyema.

We report a case of rapidly growing pleural empyema due to endobronchial lipoma. The diagnosis was established by chest computed tomography (CT). Endobronchial lipoma is a rare benign tumor of the tracheobronchial tree which can cause irreversible damage to the distal lung parenchyma if diagnosis and treatment are not carried out in time.

Validation and comparison of several published prognostic systems for patients with small cell lung cancer.

The aim of the present study was to validate and compare published prognostic classifications for predicting the survival of patients with small cell lung cancer. We pooled data from phase III randomised clinical trials, and used Cox models for validation purposes and concordance probability estimates for assessing predictive ability. We included 693 patients. All the classifications impacted significantly on survival, with hazard ratios (HRs) in the range 1.57-1.68 (all p<0.0001). Median survival times were 16-19 months for the best predicted groups, while they were 6-7 months for the most poorly predicted groups. Most of the paired comparisons were statistically significant. We obtained similar results when restricting the analysis to patients with extensive disease. Multivariate Cox models for fitting survival data were also performed. The HRs for a single covariate were 8.23 (95% CI 5.88-11.69), and 9.46 (6.67-13.50), and for extensive disease were 5.60 (3.13-9.93), 12.49 (5.57-28.01) and 8.83 (4.66-16.64). Concordance probability estimates ranged 0.55-0.65 (overlapping confidence intervals). Published classifications were validated and suitable for use at a population level. As expected, prediction at an individual level remains problematic. A specific model designed for extensive-disease patients did not appear to perform better.

Chemotherapy improves low performance status lung cancer patients.

The aim of the present study was to determine the potential benefit of conventional cisplatin-based chemotherapy on patients with advanced nonsmall cell lung cancer (NSCLC) and poor performance status (PS), defined as 60-70 on the Karnofsky scale. Retrospective analysis was carried out of a randomised trial performed in advanced NSCLC where 485 patients received three courses of gemcitabine+ifosfamide+cisplatin induction chemotherapy. Of the patients, 80% had good PS (Karnofsky 80-100) and 20% poor PS. Response rates were 38 and 28%, respectively. Clinical improvement, defined as achieving a good PS during chemotherapy, was observed overall in 25% of the poor PS patients, with rates of 38, 20 and 14%, respectively, in case of response, no change and progression. PS improved more quickly in the responders. Survival of patients with poor PS was significantly worse, but survival of responders was similar, irrespective of the initial poor or good PS. Although nonfatal toxicity was almost similar, there were more toxic deaths (including vascular and cardiac fatalities) in the poor PS patients (9.2 versus 2.1%). In conclusion, combination chemotherapy is associated with clinical improvement in a substantial number of patients with advanced nonsmall cell lung cancer of poor performance status.

Second-line paclitaxel in non-small cell lung cancer initially treated with cisplatin: a study by the European Lung Cancer Working Party.

In the context of a phase III trial comparing in advanced non-small cell lung cancer (NSCLC) sequential to conventional administration of cisplatin-based chemotherapy and paclitaxel, we evaluated the activity of paclitaxel as second-line chemotherapy and investigated any relation of its efficacy with the type of failure after cisplatin. Patients received three courses of induction GIP (gemcitabine, ifosfamide, cisplatin). Non-progressing patients were randomised between three further courses of GIP or three courses of paclitaxel. Second-line paclitaxel was given to patients with primary failure (PF) to GIP and to those progressing after randomisation to further GIP (secondary failure or SF). One hundred sixty patients received second-line paclitaxel. Response rates were 7.7% for PF and 11.6% for SF (P=0.42). Median survival times (calculated from paclitaxel start) were 4.1 and 7.1 months for PF and SF (P=0.002). In multivariate analysis, three variables were independently associated with better survival: SF (hazard ratio (HR)=1.55, 95% confidence interval (CI) 1.08-2.22; P=0.02), normal haemoglobin level (HR=1.56, 95% CI 1.08-2.26; P=0.02) and minimal weight loss (HR=1.79, 95% CI 1.26-2.55; P=0.001). Paclitaxel in NSCLC patients, whether given for primary or for SF after cisplatin-based chemotherapy, demonstrates activity similar to other drugs considered active as second-line therapy.

A phase III randomised trial comparing sequential chemotherapy using cisplatin-based regimen and paclitaxel to cisplatin-based chemotherapy alone in advanced non-small-cell lung cancer.

BACKGROUND: The purpose of this study is to determine whether in advanced non-small-cell lung cancer (NSCLC), the sequential administration of cisplatin-based chemotherapy and paclitaxel (Taxol) is superior to a cisplatin-based chemotherapy, followed by paclitaxel as salvage treatment. PATIENTS AND METHODS: A total of 485 chemotherapy naive patients with advanced NSCLC were treated with three courses of GIP (gemcitibine + ifosfamide + cisplatin), consisting of cisplatin 50 mg/m(2) on day 1, ifosfamide 3 g/m(2) on day 1 and gemcitabine 1 g/m(2) on days 1 and 8. Patients with nonprogressive disease were then randomised to further similar courses of GIP or courses of paclitaxel (225 mg/m(2) over 3 h every 3 weeks). RESULTS: Objective response or nonprogression after induction GIP occurred in 174 and 115 patients, respectively. After randomisation, there were 140 patients in the GIP arm and 141 in the paclitaxel arm. In terms of postrandomisation survival, there was no statistically significant difference (P = 0.17) between the two arms. Median times were 9.7 [95% confidence interval (CI) 7.8-11.6] and 11.9 (95% CI 9.4-14.3) months for paclitaxel and GIP, respectively. Multivariate analysis demonstrated that sex and haemoglobin were independent prognostic factors. After adjustment for these factors, the observed hazard ratio was 0.81 (95% CI 0.63-1.04) in favour of GIP (P = 0.10). Toxicity was tolerable; there was a significantly higher rate of grades III/IV thrombocytopenia with GIP and more alopecia with paclitaxel. CONCLUSION: Sequential chemotherapy using cisplatin-based regimen followed by paclitaxel does not result in better outcome than cisplatin-based chemotherapy using taxane as salvage treatment.

A phase II randomised trial comparing the cisplatin-etoposide combination chemotherapy with or without carboplatin as second-line therapy for small-cell lung cancer.

BACKGROUND: A phase II randomised trial was performed with patients with SCLC to determine if the addition of carboplatin to cisplatin-etoposide might improve the response rate in second-line therapy. PATIENTS AND METHODS: Sixty-five eligible patients were randomised: 31 for CE (cisplatin 20 mg/m(2) and etoposide 100 mg/m(2) on days 1-3) and 34 for CCE (carboplatin 200 mg/m(2) on day 1, cisplatin 30 mg/m(2) on days 2-3, etoposide 100 mg/m(2) on days 1-3). RESULTS: Eighty-two per cent of these patients had an objective response to first-line therapy and, among responders, 63% had a treatment-free interval of >3 months after previous therapy. The best response rates were 29% [95% confidence interval (CI) 13-45] and 47% (95% CI 30-64) for CE and CCE, respectively, with median survival times of 4.3 and 7.6 months. Dose-intensity analysis revealed a significant improvement in the relative dose-intensity and etoposide absolute dose-intensity for CE. Toxicity was tolerable and comparable between the two study arms. CONCLUSION: CCE appears to be associated with a high objective response rate. The phase II randomised study design suggests that a comparison between the two regimens in a phase III trial would be interesting, but will probably be difficult to perform for reasons of accrual.

A phase II study testing paclitaxel as second-line single agent treatment for patients with advanced non-small cell lung cancer failing after a first-line chemotherapy.

The purpose of this study was to determine the activity of paclitaxel as a second-line chemotherapy for non-small cell lung cancer (NSCLC). This multicentric trial included patients who had failed to a first-line chemotherapy with platinum derivatives and/or ifosfamide. After registration, patients were treated by paclitaxel i.v. at a dose of 225 mg/m(2) given over 3 h administered every 3 weeks. Response was assessed after three courses of therapy. Sixty-seven patients were registered, one was ineligible and 64 were assessable for response. Two partial responses were observed (3% of the eligible patients; 95% confidence interval: 0-7%). No change was documented in 16 cases (24%). Tolerance was acceptable, the main toxicity being cumulative polyneuropathy. Median survival duration was 4.5 months with a 1-year rate at 19%. We concluded that paclitaxel is not active in terms of response as second-line chemotherapy for NSCLC.

A three-arm phase III randomised trial assessing, in patients with extensive-disease small-cell lung cancer, accelerated chemotherapy with support of haematological growth factor or oral antibiotics.

The European Lung Cancer Working Party (ELCWP) designed a 3-arm phase III randomised trial to determine the role of accelerated chemotherapy in extensive-disease (ED) small-cell lung cancer (SCLC). Eligible patients were randomised between the 3 following arms: (A) Standard chemotherapy with 6 courses of EVI (epirubicin 60 mg m(-2), vindesine 3 mg m(-2), ifosfamide 5 g m(-2); all drugs given on day 1 repeated every three weeks. (B) Accelerated chemotherapy with EVI administered every 2 weeks and GM-CSF support. (C) Accelerated chemotherapy with EVI and oral antibiotics (cotrimoxazole). Primary endpoint was survival. 233 eligible patients were randomised. Chemotherapy could be significantly accelerated in arm B with increased absolute dose-intensity. Best response rates, in the population of evaluable patients, were, respectively for arm A, B and C, 59%, 76% and 70%. The response rate was significantly higher in arm B in comparison to arm A (P = 0.04). There was, however, no survival difference with respective median duration and 2-year rate of 286 days and 5% for arm A, 264 days and 6% for arm B and 264 days and 6% for arm C. Severe thrombopenia occurred more frequently in arm B but without an increased rate of bleeding. Non-severe infections were more frequent in arm B and severe infections were less frequent in arm C. Our trial failed to demonstrate, in ED-SCLC, a survival benefit of chemotherapy acceleration by using GM-CSF support.

Prognostic factors for patients with small cell lung carcinoma: analysis of a series of 763 patients included in 4 consecutive prospective trials with a minimum follow-up of 5 years.

BACKGROUND: The purposes of this study were to identify prognostic factors for response to chemotherapy, overall survival, and long term survival of patients with small cell lung carcinoma and to construct a classification of patients on the basis of their expected overall survival. METHODS: In the 763 patients registered in 4 consecutive clinical trials conducted by the European Lung Cancer Working Party from 1982 to 1993, the impact of 21 pretreatment variables assessable in a routine practice was analyzed for the various outcomes with a minimum follow-up of 5 years. RESULTS: The key prognostic role of disease extent was confirmed for all the outcomes. Additional independent prognostic factors for response to chemotherapy were gender, neutrophil count, and hemoglobin level; for overall survival, these factors were Karnofsky performance status, gender, and neutrophil count. Recursive partitioning and amalgamation algorithms (RECPAM) analysis classified patients into 4 groups, taking into consideration disease extent, Karnofsky performance status, age, gender, and neutrophil count. Median survival times for the 4 groups were 60, 47, 36, and 28 weeks, respectively. For long term survival, defined as a minimum survival of 2 years (9% of the patients), Karnofsky performance status was the only independent predictive factor, along with the achievement of a complete response (if this was taken into consideration). Small cell lung carcinoma remained the main cause of death among these patients. Cure was infrequent, with only 14 patients alive and disease free at 5 years (1.8%). CONCLUSIONS: In this study the long term prognosis associated with small cell lung carcinoma was poor. The well-known prognostic values of disease extent and Karnofsky performance status were confirmed, but the authors also identified age and gender (which are more controversial) as independent characteristics, in addition to citing the role of complete response in the attainment of long term survival. The independent role of neutrophils observed by the authors. must be validated by further studies.

A randomised phase III trial comparing consolidation treatment with further chemotherapy to chest irradiation in patients with initially unresectable locoregional non-small-cell lung cancer responding to induction chemotherapy. European Lung Cancer Working Party.

PURPOSE: A phase III randomised trial was conducted in patients with non-metastatic unresectable non-small-cell lung cancer in order to compare, in responders to induction chemotherapy, consolidation treatment by further chemotherapy to chest irradiation. PATIENTS AND METHODS: A total of 462 untreated NSCLC patients were eligible for three courses of induction chemotherapy (MIP) consisting of cisplatin (50 mg/m2), ifosfamide (3 g/m2) and mitomycin C (6 mg/m2). It was proposed that objective responders be randomised to either three further courses of MIP or to chest irradiation (60 Gy; 2 Gy per fraction given over six weeks). RESULTS: An objective response rate of 35% was achieved; 115 patients (including 52% with initial stage IIIA and 44% with initial stage IIIB) were randomised to consolidation treatment, 60 of them to further chemotherapy and 55 to chest radiotherapy. There was no significant difference in survival between the two arms, with a respective median and two-year survival of 42 weeks (95% confidence intervals (95% CI: 35-51) and 18% (95% CI: 8-28) for chemotherapy and 54 weeks (95% CI: 43-73) and 22% (95% CI: 11-33) for irradiation. There was also no statistical difference for response duration between the two arms but chest irradiation was associated with a significantly greater duration of local control than chemotherapy (median duration times: 158 vs. 31 weeks, P = 0.0007). CONCLUSIONS: For non-metastatic unresectable NSCLC treated by an induction chemotherapy regimen containing cisplatin and ifosfamide, if an objective response is obtained, consolidation treatments by further chemotherapy or by chest irradiation result in non-statistically different survival distributions, although a better local control duration is observed with radiotherapy.

[Diagnosis of intralobar pulmonary sequestration using helical computed tomography angiography: apropos of 3 patients]. / Diagnostic de la sequestration pulmonaire intralobaire par angio-TDM helicoidale: a propos de 3 patients.

Pulmonary sequestration is a rare congenital anomaly that consists of abnormal pulmonary tissue for which the arterial supply is usually derived from the aorta or its major branches. Considering clinical and anatomical aspects two types of sequestration, intralobar and extralobar, have been described. The definite diagnosis requires exact visualization of the anomalous feeding and draining vessels and this condition is essential when surgical treatment is necessary because of recurrent pulmonary infections. We report on 3 cases of intralobar sequestration successfully and extensively diagnosed in adults by spiral angioCT. Our series includes one symptomatic left case confirmed by surgery and two rare fortuitous asymptomatic right cases. In the three cases, the pulmonary abnormal tissue, the arterial supply and venous drainage were clearly identified. We conclude that, probably more than MRI, spiral angio-CT can presently be considered the first choice procedure to diagnose and evaluate pulmonary sequestration; the equal performance of spiral CT in imaging lung and vessels makes classical angiography unnecessary.

Evaluation of the TN sub-staging in patients with initially unresectable stage III non-small cell lung cancer treated by induction chemotherapy. The European Lung Cancer Working Party.

PURPOSE: This study attempted to investigate, in a cohort of patients with clinical stage III initially unresectable non-small cell lung cancer (NSCLC) treated by the same induction chemotherapy regimen, the prognostic value of clinical T and N sub-groupings in order to validate the current International Staging System (ISS). PATIENTS AND METHODS: All the eligible patients with stage III NSCLC (428 patients) registered in a clinical trial were included in the study investigating, after three courses of induction chemotherapy, the role, in responders, of chest irradiation in comparison to further chemotherapy. The chemotherapy regimen consisted of mitomycin C, ifosfamide and cisplatin. RESULTS: Patients with ISS 1986 stage IIIA had a significantly better survival than those with stage IIIB (median survival 47 vs 36 weeks; P = 0.01). A RECPAM analysis showed that patients with T1-T2 N3 and T4 N0-1-2 stage had a more similar prognosis to those with stage IIIA. That result leads to define two new sub-groups: stage IIIlalpha (T3-T4 N0-N1; any T N2; T1-T2 N3) and IIIbeta (T3-T4 N3), with a highly significant difference in survival between them (median survival: 45 vs 29 weeks; P < 0.0001). The superiority of that new classification on the ISS documented in our series of stage III patients for discriminating survival and tumour response has to be confirmed on another series in a multivariate context. CONCLUSION: For unresectable NSCLC treated by induction chemotherapy, stage III sub-classification by moving T4 N0-1 and T1-2 N3 tumours from stage IIIB to stage IIIA appeared to better correlate with prognosis. The usefulness of this new sub-division has to be tested in validation studies.

[Prognostic factors in advanced stage non-small cell bronchial cancer: experiences of the European Lung Cancer Working Party]. / Facteurs pronostiques des cancers bronchiques non à petites cellules au stade avancé: expérience de l'European Lung Cancer Working Party.

The European Lung Cancer Working Party has investigated prognostic factors for response, overall survival, long term survival in a population with advanced non small cell lung cancer registered in a clinical trial evaluating platinum derivatives-containing chemotherapy regimens. Various factors have been identified in multivariate analyses and were classified using RECPAM methodology. In addition to the clinical factors such as disease extent and performance status were shown, as significant predictors, rarely studied biological factors like pretherapeutic leucocyte and polynuclear levels. The obtention of an objective response to chemotherapy appeared to be a major prognostic factor for further survival.

Response to chemotherapy has predictive value for further survival of patients with advanced non-small cell lung cancer: 10 years experience of the European Lung Cancer Working Party.

The aim of this study was the assessment of the predictive value for survival of an antitumoral response to three courses of chemotherapy in association with various pretreatment characteristics in patients with non-resectable non-small cell lung cancer treated by cisplatin- (or carboplatin)-based combination regimens. Patients considered for this study were eligible patients with advanced non-small cell lung cancer registered in one of the seven trials conducted by the European Lung Cancer Working Party from December 1980 to August 1991. All these trials tested chemotherapy regimens with platinum derivatives (cisplatin and/or carboplatin). In this population of 1052 eligible patients, 752 were assessed in this analysis. Data were prospectively collected on 23 pretherapeutic variables and objective response after three chemotherapy cycles. The predictive value of response to chemotherapy on survival (measured from the time of response assessment i.e. 12 weeks after registration in the trial) was studied by univariate analysis as well as by multivariate methods (adjustment of the impact of several covariates simultaneously on the dependent variable) with adjustment for the pretreatment prognostic variables. After three cycles of chemotherapy, the global estimated median survival time was 24 weeks with a 95% confidence interval of 22-25 weeks. By univariate analysis, we identified an objective response to chemotherapy as a highly significant discriminant marker (P < 0.0001) for further survival with estimated median survival times of 41 weeks (95% CI: 38-46) and 19 weeks (95% CI: 17-20), respectively, for the responding and non-responding patients. In a Cox regression model fitted to the data using a forward stepwise procedure, this variable was the first selected explanatory variable. Its effect was adjusted by the introduction in the model of initial disease extent, Karnofsky performance status, serum calcium level and white blood cell count. These results were consistent with those obtained by application of recursive partitioning and amalgamation algorithms (RECPAM) which led to a classification of the patients into three homogeneous subgroups. Our results, using a classical Cox regression model consistent with those highlighted by application of a RECPAM analysis, found an objective response to chemotherapy to be a predominant predictive factor for further survival, although it did not allow any conclusion about a causal relationship. The RECPAM results led to a classification of the patients into three subgroups which needs to be validated in other series.

Prognostic factors for response to chemotherapy containing platinum derivatives in patients with unresectable non-small cell lung cancer. (NSCLC).

PURPOSE: To identify pretreatment variables predicting response to platinum derivatives containing chemotherapy in patients with unresectable non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Eligible patients included in one of the 7 consecutive clinical trials conducted by the European Lung Cancer Working Party between December 1980 and August 1991. All patients received a cisplatin or carboplatin containing chemotherapy. We analyzed 22 potential prognostic factors including sex, age, histology, performance status, weight loss, type of lesions, extent of disease, main metastatic sites and several biological parameters, namely white blood cell count (WBC), neutrophil count, platelet count, hemoglobinemia, creatininemia, serum alkaline phosphatases and LDH. RESULTS: On 1052 eligible patients. 107 were not assessable for response. The objective response rate was 26% (95% C.I.: 23, 29%). Univariate analysis identified as statistically significantly associated with a higher objective antitumoral response rate the following characteristics: a normal platelet count, the absence of skin metastasis, the absence of adrenal metastasis, a higher creatininemia, a normal hemoglobinemia, an older age and a normal WBC count. On a restricted set of variables including data from 777 patients, a multivariate logistic regression model disclosed age and platelet count as significantly and independently related to response rate. CONCLUSION: Clinical and demographic characteristics of patients with unresectable NSCLC, as well as routine laboratory parameters, could not accurately predict response to chemotherapy in a population of patients selected for a clinical trial. Future studies on this subject should include more sophisticated variables as new biomolecular makers.

Randomized trial comparing induction chemotherapy versus induction chemotherapy followed by maintenance chemotherapy in small-cell lung cancer. European Lung Cancer Working Party.

PURPOSE AND METHODS: The European Lung Cancer Working Party (ELCWP) performed a randomized trial with the primary end point to determine if maintenance chemotherapy with 12 courses of etoposide (120 mg/m2 on days 1 and 3) and vindesine (3 mg/m2 on day 3) could improve progression-free survival in small-cell lung cancer (SCLC) patients who responded to six courses of induction chemotherapy with ifosfamide, etoposide, and an anthracycline (doxorubicin or epirubicin). RESULTS: Among 235 eligible patients initially registered, 91 were randomized to receive maintenance therapy, including seven patients who were no longer responding. Among 84 randomized responders, progression-free survival was significantly improved (P = .003) by maintenance therapy, with median durations (maintenance v follow-up) of 25 versus 12 weeks after the second randomization, but survival was not significantly increased (P = .10), with median durations of 48 and 38 weeks. However, in a multi-variate analysis that took into account disease extent, maintenance therapy, Karnofsky performance status (PS), and absolute dose-intensity (ADI) of anthracycline given during induction, limited disease (LD) and maintenance were found to be independent positive predictors of survival. CONCLUSION: We conclude that maintenance chemotherapy in responding patients is beneficial in SCLC.

Prognostic factors for survival in advanced non-small-cell lung cancer: univariate and multivariate analyses including recursive partitioning and amalgamation algorithms in 1,052 patients. The European Lung Cancer Working Party.

PURPOSE: This study attempted to determine the prognostic value for survival of various pretreatment characteristics in patients with nonresectable non-small-cell lung cancer in the context of more than 10 years of experience of a European Cooperative Group. PATIENTS AND METHODS: We included in the analysis all eligible patients (N = 1,052) with advanced non-small-cell lung cancer registered onto one of seven trials conducted by the European Lung Cancer Working Party (ELCWP) during one decade. The patients were treated by chemotherapy regimens based on platinum derivatives. We prospectively collected 23 variables and analyzed them by univariate and multivariate methods. RESULTS: The global estimated median survival time was 29 weeks, with a 95% confidence interval of 27 to 30 weeks. After univariate analysis, we applied two multivariate statistical techniques. In a Cox regression model, the selected explanatory variables were disease extent, Karnofsky performance status, WBC and neutrophil counts, metastatic involvement of skin, serum calcium level, age, and sex. These results were confirmed by application of recursive partitioning and amalgamation algorithms (RECPAM), which led to classification of the patients into four homogeneous subgroups. CONCLUSION: We confirmed by our analysis the role of well-known independent prognostic factors for survival, but also identified the effect of the neutrophil count, rarely studied, with the use of two methods: a classical Cox regression model and a RECPAM analysis. The classification of patients into the four subgroups we obtained needs to be validated in other series.

Induction chemotherapy with ifosfamide, etoposide, and anthracycline for small cell lung cancer: experience of the European Lung Cancer Working Party.

Prospective trials comparing drug analogues in the treatment of small cell lung cancer are rare. The European Lung Cancer Working Party has conducted a randomized trial with a primary end point of determining the effect on survival of maintenance chemotherapy and a secondary end point of comparing doxorubicin (45 mg/m2) with a bioequivalent epirubicin dose (60 mg/m2) in one set of patients, and a standard with a high epirubicin dose (60 v 90 mg/m2) in a second set of patients. Anthracycline was given on day 1 of induction chemotherapy in combination with ifosfamide (1.5 g/m2 intravenously days 1 through 3) and etoposide (80 mg/m2 intravenously days 1 through 3). Six courses were given at 3-week intervals. In all, 235 eligible previously untreated patients with pathologically proven small cell lung cancer were randomized: 106 to the comparison of doxorubicin and epirubicin and 129 to the comparison of standard-dose versus high-dose epirubicin. There was no difference between the regimens in terms of objective response rate or survival, and the regimen containing the lower (60 mg/m2) epirubicin dose was better tolerated, with fewer toxic deaths and less need for dose and schedule adjustments.