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B Salvadori

Publications and source records attributed to B Salvadori.

At least 19 recordsLinked to original sources
PubMed1999

Reoperation for locally recurrent breast cancer in patients previously treated with conservative surgery.

BACKGROUND: This study aimed to analyse the possibility of surgical rescue of intrabreast tumour recurrence (IBTR) following conservative operation for breast cancer, i.e. quadrantectomy, axillary dissection and radiotherapy. METHODS: Of 2544 patients treated with this approach, 209 presented with an IBTR as the first and only sign of relapse. Some 197 patients were considered suitable for further surgery; 12 were inoperable. Six patients declined operation. RESULTS: Reoperative surgery was total mastectomy in 134 patients (70 per cent) and further local resection in 57 (30 per cent). Median follow-up after second surgery was 73 (range 1-192) months. The overall survival probability at 60 months was 70 per cent after mastectomy and 85 per cent following further local excision. There was no difference in disease-free survival between the two operative groups. Second IBTR was more common at 5 years in the re-excision group (19 versus 4 per cent). CONCLUSION: Since the type of surgery did not seem to affect survival, breast conservation can be considered in selected patients with IBTR.

Breast Neoplasms↗
PubMed1998

Ten year results of a randomised trial comparing two conservative treatment strategies for small size breast cancer.

We report the 10-year results of a randomised clinical trial in which two different breast conservation treatment strategies were compared in women with small, non-metastatic primary breast cancer: quadrantectomy, axillary dissection and radiotherapy (QUART) versus tumorectomy and axillary dissection followed by external radiotherapy and a boost with 192Ir implantation (TART). No second surgery was given to women with affected surgical margins. Axillary node positive women received adjuvant medical therapy. From 1985-1987, this trial accrued 705 patients, 360 in the QUART and 345 in the TART arm. Crude cumulative incidence curves for intrabreast tumour recurrence (IBTR) and metastases as first events and mortality curves in each of the two treatment arms were computed. A crude cumulative incidence curve of IBTR as a second event (in women who had already had a local recurrence) was also computed. The two groups were compared in terms of hazard for IBTR, metastases or death occurrence by using Cox regression models, both with and without adjustment for patient age, tumour size, number of metastatic axillary nodes and histology. Possible interactions between the aforementioned prognostic factors and the type of surgery were also investigated. The two groups were well matched for baseline patient and tumour characteristics, the only exception being resection margins, which were more often positive in the TART group. At the Cox model, a significant difference between groups was detected for IBTR (P < 0.0001), but not for distant metastases and overall survival. In particular, 5- and 10-year estimates of crude cumulative incidence of IBTR were 4.7 and 7.4% in the QUART group and 11.6 and 18.6% in the TART group. The difference was not substantially affected by patient or disease characteristics. Likewise, the status of resection margins in women who underwent TART treatment did not significantly influence the risk of occurrence of IBTRs. Finally, the rate of second IBTR occurrence was relatively high, when compared with the rate of IBTR occurrence as first event. In summary, the results of this trial show that a better local control of the disease can be obtained with the more extensive surgical resection, i.e. QUART.

Adult↗
PubMed1998

Prospective evaluation of fluorine-18-FDG PET in presurgical staging of the axilla in breast cancer.

METHODS: The presurgical, noninvasive staging of axillary nodes for metastases was prospectively investigated in 68 patients who were diagnosed with primary breast cancer using PET with 18F-fluorodeoxyglucose (FDG). Four patients had bilateral nodules; therefore, the total number of evaluable cases was 72. Visual analyses of attenuation-corrected PET images and standardized uptake values (SUVs) of FDG uptake in carcinomas were compared with histopathological surgical findings. The SUV distribution differences between carcinomas with and without axillary metastases were evaluated by means of statistical and receiver operating characteristics analyses. RESULTS: PET correctly classified 64 of the 72 cases; four false-positive and four false-negative PET results were found. The overall sensitivity, specificity and accuracy of PET for axillary metastases were 85%, 91% and 89%, respectively. With respect to the clinical axillary stage of the patients (TNM, or tumor-node-metastasis, classification), we obtained the following results: N0 patients, sensitivity = 70%, specificity = 92%, accuracy = 86%; N1a patients, sensitivity = 85.5%, specificity = 100%, accuracy = 95%; and N1b-2 patients, sensitivity = 100%, specificity = 67%, accuracy = 87%. The median SUV in carcinomas with axillary metastases (4.6) was significantly higher than that in carcinomas without metastases (2.9), but there was a great SUV overlap between the two groups (interquartile ranges = 2.7-7.2 and 1.9-4.5, respectively). Analysis of the receiver operating characteristics curve showed that a high sensitivity of SUV in predicting axillary metastases was associated with a very low specificity and vice versa. With the best SUV cutoff value of 2.9, the sensitivity and specificity were 74% and 56%, respectively. CONCLUSION: PET showed good overall diagnostic accuracy in the detection of axillary metastases (86%). The very high accuracy (95%) in N1a patients is of particular importance. False-negative PET findings, however, can be encountered. SUVs of breast carcinoma cannot predict the spread of the disease to the axilla, even if higher values are often associated with axillary metastases. Any decision on the use of PET in the presurgical staging of breast cancer should be incorporated into a more general debate on axillary management. In selected patients with a very low probability of axillary metastases (T1a), in whom axillary surgery can already be avoided according to data from follow-up studies, 18F-FDG PET could be proposed as a noninvasive imaging modality to improve the diagnosis of axillary relapses.

Axilla↗
PubMed1998

Paclitaxel plus epirubicin in advanced breast cancer.

This phase I-II study aimed to determine the maximum tolerated dose (MTD) of paclitaxel (Taxol), infused over 3 hours, when combined with a fixed dose (90 mg/m2) of epirubicin. Other aims were to investigate the combination's plasma pharmacokinetics, toxicity, and activity in 50 patients with previously untreated metastatic breast cancer, as well as its ability to mobilize peripheral blood stem cells (PBSCs). The initial dose of paclitaxel, 135 mg/m2, was increased by 20 mg/m2 in subsequent cohorts of six patients until dose-limiting toxicity (DLT) occurred. The DLT of the combination was febrile neutropenia in two of eight patients who received paclitaxel at 225 mg/m2. The concentration of epirubicinol, the major metabolite of epirubicin, decreased from 47.3 +/- 9.4 ng/mL at 175 mg/m2 of paclitaxel to 37.9 +/- 7.5 ng/mL at the 225-mg/m2 dose. The most relevant toxicity was grade 4 neutropenia (61% of all the courses). Cardiac toxicity included three patients (6%) developing congestive heart failure responsive to therapy. Among 49 evaluable patients, 41 responses (84%) were observed (95% confidence interval [CI], 70% to 92%) and 9 (19%) of these were complete. In 21 patients, we evaluated the mobilization of PBSCs after this regimen plus a colony-stimulating factor. The median number of CD34+ cells was 61.7/microL (range, 6.8 to 201/microL), and a median of 6.3 x 10(6)/kg of CD34+ cells have been harvested with a single leukapheresis.

Antibiotics, Antineoplastic↗
PubMed1997

Cell proliferation in 3,800 node-negative breast cancers: consistency over time of biological and clinical information provided by 3H-thymidine labelling index.

For breast cancer, many prognostic markers that initially appeared promising have failed to maintain their clinical predictive value. Few reports have analyzed the consistency over time of biological and clinical information provided by biomarkers. Tumour cell proliferation has acquired relevance as an indicator of prognosis and of response to treatment. Since its clinical role has been investigated for some decades, cell proliferation represents an ideal marker for an over-time validation. In 3,800 node-negative breast cancers recruited between 1972 and 1991, the consistency of information provided by the 3H-thymidine labelling index (TLI), in terms of basic relations with other clinico-pathological and biological variables and clinical predictivity, was evaluated using a combined analysis of results previously published by our group for distinct series of patients. Clinical predictivity was analyzed on a subset of 2,067 patients given local-regional therapy until relapse and followed for a median time from 6 to 10 years. Over the entire period TLI maintained a weak direct relation with tumour size and an inverse strong relation with steroid receptors. An increase in TLI was observed for tumours in post-menopausal patients up to the mid 1980s. During 3 different accrual periods (1972-1983; 1984-1987; 1988-1991), TLI was a consistent and independent predictor of relapse-free time, distant metastasis and overall survival, regardless of its consideration as a continuous variable or with a cutoff value of 3%. The reproducibility of our results over time provides support to the consistency of the methodology used and of the biological and clinical information obtained when using TLI as an indicator of breast cancer cell proliferation.

Adult↗
PubMed1997

Clinical target volume localization using conventional methods (anatomy and palpation) and ultrasonography in early breast cancer post-operative external irradiation.

PURPOSE: To evaluate the accuracy of three methods, anatomy (A), palpation (P) and ultrasounds (US) in localizing the clinical target volume (CTV) in patients (pts) with early breast cancer (EBC) undergoing breast external irradiation as part of conservation therapy. MATERIAL AND METHODS: One hundred consecutive pts with EBC (T(is) 1%, T1 78%, T2 21%, N- 68%, N+ 32%), treated with conservation surgery and breast irradiation with opposed tangential portals, were prospectively analyzed. Anatomically, palpatory or ultrasound defined field borders for CTV localizations were determined in the same position thanks to the utilization of a vacuum-formed cellulose acetate immobilization cast, removed during CTV definitions. RESULTS: P and US CTV localizations have been found to coincide on the four margins (superior, inferior, medial, lateral) in only 1/100 pts, while no pt showed identical A and US CTV localizations. Only 31/397 (8%) field measurements with A, and 98/395 (25%) with P corresponded to US border definition. If mean and median values of each field border were considered, the CTV was generally overestimated with P appearing more accurate than A in a gross definition of the target (P < 0.01). However, a geographical miss of at least one field border of CTV occurred in 55% of pts with A and in 36% of pts with P. The most critical margin to be defined with conventional methods was the superior one: an underestimation of the cranial border of CTV with A was observed in 51% and with P in 22% of pts (22% and 8%, respectively, when an underestimation by more than 1.5 cm was considered). When pre-menopausal and peri/post-menopausal groups of pts were separately analyzed, conventional methods were highly inaccurate to define the superior border in younger pts, in which a geographical miss was noted with A in 62% and with P in 35% of cases (P < 0.05). When an underestimation of more than 1.5 cm was evaluated, these values were reduced to 33% and 12%, respectively (P = 0.02). Also, in the subgroup of pre-menopausal patients the CTV defined by palpatory reference lines appeared to be more accurate than A-method (P < 0.01). CONCLUSIONS: Conventional methods frequently appear inadequate to localize residual mammary gland in EBC post-operative external irradiation. This analysis evidentiates the inaccuracy of empirical CTV definition, and suggests that palpation or anatomical reference borders should be critically used and that state of art imaging methods should be included in treatment planning, particularly in pre-menopausal pts. If economical or individual variables have to be taken into account, palpation might be considered in post-menopausal women.

Adult↗
PubMed1997

Prognostic factors for metachronous contralateral breast cancer: a comparison of the linear Cox regression model and its artificial neural network extension.

The purpose of the present study was to assess prognostic factor for metachronous contralateral recurrence of breast cancer (CBC). Two factors were of particular interest, namely estrogen (ER) and progesterone (PgR) receptors assayed with the biochemical method in primary tumor tissue. Information was obtained from a prospective clinical database for 1763 axillary node-negative women who had received curative surgery, mostly of the conservative type, and followed-up for a median of 82 months. The analysis was performed based on both a standard (linear) Cox model and an artificial neural network (ANN) extension of this model proposed by Faraggi and Simon. Furthermore, to assess the prognostic importance of the factors considered, model predictive ability was computed. In agreement with already published studies, the results of our analysis confirmed the prognostic role of age at surgery, histology, and primary tumor site, in that young patients (< or = 45 years) with tumors of lobular histology or located at inner/central mammary quadrants were at greater risk of developing CBC. ER and PgR were also shown to have a prognostic role. Their effect, however, was not simple in relation to the presence of interactions between ER and age, and between PgR and histology. In fact, ER appeared to play a protective role in young patients, whereas the opposite was true in older women. Higher levels of PgR implied a greater hazard of CBC occurrence in infiltrating duct carcinoma or tumors with an associated extensive intraductal component, and a lower hazard in infiltrating lobular carcinoma or other histotypes. In spite of the above findings, the predictive value of both the standard and ANN Cox models was relatively low, thus suggesting an intrinsic limitation of the prognostic variables considered, rather than their suboptimal modeling. Research for better prognostic variables should therefore continue.

Adult↗
PubMed1997

Efficacy, toxicity, and applicability of high-dose sequential chemotherapy as adjuvant treatment in operable breast cancer with 10 or more involved axillary nodes: five-year results.

PURPOSE: To assess the efficacy, toxicity, and applicability of high-dose therapy administered as adjuvant initial treatment to women with breast cancer with extensive nodal involvement. PATIENTS AND METHODS: Sixty-seven patients with stage II to III breast cancer involving > or = 10 axillary nodes received a novel high-dose sequential (HDS) regimen, including the high-dose administration of three non-cross-resistant drugs (cyclophosphamide, methotrexate, and melphalan) given within the shortest interval of time as possible with hematologic and nonhematologic toxicity. RESULTS: Sixty-three patients completed the program as planned, one patient died of acute toxicity, and three patients were switched to standard-dose adjuvant therapy. After a median follow-up duration of 48.5 months and a lead follow-up of 78 months, actuarial relapse-free survival for all 67 registered patients is 57% and overall survival is 70%, respectively. Comparison with a historical control group of 58 consecutive patients showed a significantly superior rate of freedom from relapse for the HDS-treated group (57% v 41%, respectively), in particular when two subgroups of patients, more homogeneous for their number of involved nodes, were compared (65% v 42%). Overall, treatment was of short duration (median, 70 days), required a median of 32 days of hospital stay, and was associated with only a few severe side effects (the most distressing being oral mucositis after melphalan therapy). CONCLUSION: HDS therapy emerges as an effective and applicable regimen, whose major toxicity was occasional. Final assessment of its value in a randomized, multicenter trial is presently underway.

Adult↗
PubMed1997

Dose-finding study and pharmacokinetics of epirubicin and paclitaxel over 3 hours: a regimen with high activity and low cardiotoxicity in advanced breast cancer.

PURPOSE: To determine the maximum-tolerated dose (MTD) of paclitaxel over 3 hours with a fixed dose of epirubicin, to investigate the plasma pharmacokinetics of this combination, and to evaluate the toxicity and the activity in previously untreated metastatic breast cancer patients. PATIENTS AND METHODS: Fifty patients with metastatic breast cancer, measurable disease, and normal left ventricular ejection fraction (LVEF) were eligible. Epirubicin was administered as an intravenous (I.V.) bolus at the fixed dose of 90 mg/m2 before the infusion of paclitaxel over 3 hours. The initial dose of paclitaxel was 135 mg/m2 and was increased by 20 mg/m2 in subsequent cohorts of six patients until dose-limiting toxicity (DLT). Plasma pharmacokinetics of paclitaxel and epirubicin was performed at cycle 1 in at least two patients per dose level of paclitaxel (175 up to 225 mg/m2). RESULTS: The DLT of this combination was febrile neutropenia in two of eight patients who received paclitaxel at 225 mg/m2. The mean peak plasma concentration of paclitaxel ranged between 5.1 and 6.2 micromol/L at doses of 175 to 225 mg/m2. The concentration of epirubicinol decreased from 47.3 +/- 9.4 to 37.9 +/- 7.5 ng/mL in patients treated with paclitaxel 175 and 225 mg/m2. The most relevant toxicity was grade 4 neutropenia (61% of all courses). The pharmacokinetic data of paclitaxel, in particular the time above the threshold level of 0.05 micromol/L, were not significantly related to myelosuppression. Cardiac toxicity was mild: three patients (6%) developed mild congestive heart failure that was responsive to therapy. Among 49 assessable patients, 41 responses (84%; 95% confidence interval [CI], 70% to 92%) were observed, and nine (18%) of these were complete. CONCLUSION: Our study demonstrates that (1) the MTD is epirubicin 90 mg/m2 and paclitaxel 200 mg/m2; (2) no clear relationship exists between pharmacokinetic data of paclitaxel and myelosuppression, while the increase in the dose of paclitaxel is associated with a reduction in epirubicinol plasma levels; and (3) the association is feasible, with low cardiotoxicity, and has a high activity in metastatic breast cancer.

Adult↗
PubMed1997

Conservative surgery for infiltrating lobular breast carcinoma.

BACKGROUND: Some reports state that infiltrating lobular breast carcinoma (ILC) should not be treated by conservative methods because of a high risk of local recurrence. The aim of this study was to determine whether patients with conservatively treated ILC have a higher risk of intrabreast relapse than those with infiltrating ductal carcinoma (IDC). METHODS: Some 286 consecutive patients with ILC of the breast were compared with 1903 women with IDC treated at the Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, over the same interval (1973-1989). Patients in both series received the same treatment: quadrantectomy, complete axillary dissection and radiotherapy to the breast. Adjuvant treatment was administered according to nodal and menopausal status (chemotherapy or tamoxifen). Follow-up lasted until December 1994, with a median of 137 months for patients with ILC and 133 for those with IDC. Histology slides were reviewed to assess the presence of multifocality (ILC 4.5 per cent versus IDC 3.6 per cent and extensive intraduct component (ILC 0.3) per cent versus IDC 6.4 per cent). RESULTS: No difference in cumulative local recurrence rate was found between the two groups at 10 years (approximately 7 per cent). CONCLUSION: Conservative surgery is equally safe for patients with infiltrating lobular or ductal carcinoma of the breast.

Breast Neoplasms↗
PubMed1997

Pilot study of primary chemotherapy with doxorubicin plus paclitaxel in women with locally advanced or operable breast cancer.

A pilot study of primary chemotherapy with bolus doxorubicin plus paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) infused over 3 hours was performed in 38 women with locally advanced and 41 with stage II/III breast cancer. Patients received four cycles of primary chemotherapy followed by surgery and treatment with cyclophosphamide/methotrexate/5-fluorouracil for six cycles. Preliminary data are available on 73 patients. Doxorubicin plus paclitaxel was well tolerated. Primary toxicity consisted of grade 1 or 2 reversible peripheral neuropathy and grade 3 alopecia. After a median follow-up of 13 months, none of the patients have developed cardiac toxicity or any significant alteration of the left ventricular ejection fraction, which was measured before treatment, at each cycle of doxorubicin plus paclitaxel, and every 3 months thereafter. Major clinical response of the breast tumor was observed in 88% of patients. At pathologic examination of the surgical specimen, 40% were pT1, 15% had no macroscopic tumor residue, and 7% had complete disappearance of invasive neoplastic cells. After a median follow-up of 17 months for patients with locally advanced breast cancer, freedom from progression was 67%, disease-free survival was 71%, and overall survival was 74%. The same end points were 100% for patients with stage II/III disease, with a shorter median follow-up of 10 months. In conclusion, doxorubicin plus paclitaxel is safe, feasible, and effective, and can be used as primary or adjuvant chemotherapy to assess its actual therapeutic role in women with early breast cancer.

Adult↗
PubMed1997

Lymphoid infiltration as a prognostic variable for early-onset breast carcinomas.

Infiltration by lymphoid cells is a common feature of many human tumors, including breast carcinomas, and the degree of infiltration has been suggested to be a measure of the host immune response. Our analyses in a series of 1919 cases of primary ductal and lobular infiltrating breast carcinomas from women with a long-term follow-up revealed: (a) a 16-17% frequency of infiltrated tumors independent of the patient's age at diagnosis; and (b) a strong positive correlation between survival rates and the presence of lymphocytes at the tumor site in patients less than 40 years of age (P = 0.0002) but no association with prognosis in patients 40 years of age or older. Multivariate analysis indicated that lymphoid infiltration is independent of other conventional prognostic factors such as nodal status and tumor size in predicting survival. Thus, a possible immune response against the tumor seems to be relevant only in women with early-onset tumors. Because the immune system is functionally maximum in younger years, declining with age, this finding might reflect a difference in the efficiency of the immune system. Alternatively, the biology of these tumors might differ, leading to a difference in immuno-genicity.

Adult↗
PubMed1996

Results of a breast-cancer-surgery trial compared with observational data from routine practice.

BACKGROUND: The strength of randomised controlled trials (RCTs) is that they allow investigators to draw reliable inferences about treatment differences; physicians can then make a choice between different options. Their weakness is that they are conducted on a set of patients who cannot be regarded as a random sample from the population that will be treated outside the trial. Observational data collected in a prospective clinical database may provide more realistic estimates. METHODS: At the Istituto Nazionale de Tumori of Milan an RCT was started in 1973 (MI1) in which Halsted mastectomy was compared with quadrantectomy plus axillary dissection and radiotherapy (QUART), a breast conserving treatment, for "early-stage" primary breast cancer. In addition, a prospective clinical database was established to collect, in standard format, information on all women undergoing breast conservation thereafter and followed up at the Institute. 1760 women were treated with QUART, 350 of them being accrued in the years 1973-80 in the context of the MI1 trial. The remaining 1408 received QUART after the MI1 trial, up to December, 1984. RESULTS: In the years after the trial, the criteria for use of QUART became more liberal. However, after adjustment for baseline characteristics, out-trial patients fared no worse than trial patients in terms of survival or distant metastasis. Out-trial patients did have a slightly higher rate of local recurrence, probably because of subtle and multiple changes in the surgical procedures since the time of the trial. INTERPRETATION: The results of QUART in out-trial patients resembled those reported from research settings. In this instance, the results of clinical trials did not exaggerate the benefits obtainable in routine practice.

Adult↗
PubMed1996

Paclitaxel and vinorelbine in anthracycline-pretreated breast cancer: a phase II study.

BACKGROUND: Paclitaxel and vinorelbine are active in advanced breast cancer pretreated with anthracyclines We therefore conducted a phase II study to define the toxicity and activity of paclitaxel and vinorelbine administered in combination. PATIENTS AND METHODS: Our patient population consisted of 37 patients with metastatic breast cancer, 35 of whom had received prior chemotherapy including anthracyclines. The treatment regimen included vinorelbine (25 mg/m2 i.v.) followed by paclitaxel (135 mg/m2 i.v. as a 3-hour infusion) on day 1; vinorelbine was repeated on day 8 in the first 14 patients and on day 3 in the remaining 23 patients. RESULTS: Because of grade 4 neutropenia, the second dose of vinorelbine was reduced or omitted in 88% of the courses on the days 1 and 8 schedule and in 48% of the courses on the days 1 and 3 schedule. As a consequence the administered dose intensity of vinorelbine was significantly higher on the days 1 and 3 schedule (13 mg/m2/wk versus 8.3 mg/m2/ wk, P = 0.005). The overall response rate was 38% (95% CI: 22-55); four responses have been observed in the ten patients with absolute anthracycline resistance. The median duration of response was 6.5 months. CONCLUSIONS: The combination of paclitaxel and vinorelbine is a feasible and active salvage regimen in advanced breast cancer patients pretreated with anthracyclines.

Adult↗
PubMed1996

p53 and bcl-2 expression correlates with clinical outcome in a series of node-positive breast cancer patients.

BACKGROUND AND PURPOSE: The tumor-suppressor gene TP53 and the proto-oncogene bcl-2 encode, respectively, for a nuclear phosphoprotein and for a mitochondrial protein involved in multiple cellular functions. The proteins provide prognostic information in node-negative breast cancer and are supposed to influence treatment responsiveness. We analyzed the predictive role of p53 and bcl-2 expression, alone and in association with other variables, in postmenopausal women with node-positive, estrogen receptor-positive (ER+) breast cancers treated with radical or conservative surgery plus radiotherapy and adjuvant tamoxifen for at least 1 year. PATIENTS AND METHODS: On 240 resectable cancers, we determined the expression of p53 and bcl-2, using immunohistochemistry, cell proliferation (3H-thymidine labeling index [3H-dT LI]), and ER and progesterone receptors (PgR). RESULTS: p53 expression and 3H-dT LI were weakly related to one another and both were unrelated to bcl-2. Relapse-free and distant metastasis-free survival at 5 years were significantly lower for patients with tumors that highly expressed p53 (P = .0001) and for those that weakly expressed or did not express bcl-2 (P = .02). However, p53, but not bcl-2, provided prognostic information independent of tumor size, axillary node involvement, steroid receptors, and 3H-dT LI. Moreover, the simultaneous p53 overexpression and lack of PgR identified patients at maximum risk of relapse, whereas bcl-2 overexpression, associated with a low 3H-dT LI or the presence of PgR, improved the prognostic resolution for low-risk patients. CONCLUSION: p53 expression appears to be indicative of clinical outcome in postmenopausal patients treated with tamoxifen. Whether p53 overexpression and weak bcl-2 expression are indicators of biologic aggressiveness, regardless of treatment, or of hormone resistance remains to be defined.

Aged↗
PubMed1996

Activity and safety of epirubicin plus paclitaxel in advanced breast cancer.

We performed a dose-escalation study to evaluate the maximum tolerated dose (MTD) of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) plus a fixed dose of epirubicin. Epirubicin was administered as a 90 mg/m2 bolus immediately followed by a 3-hour infusion of paclitaxel starting at 135 mg/m2 and escalating by 20mg/m2 for each triplet of patients as long as no dose-limiting toxicity had occurred; courses were repeated every 3 weeks. The MTD was defined as that at which any of the following toxicities occurred in at least two of six patients: absolute neutrophil count less than 500/microliter for more that 7 days or less than 100/microliter for more than 3 days; any episode of febrile neutropenia requiring intravenous antibiotics and hospitalization; grade 4 thrombocytopenia requiring platelet transfusion; failure to recover absolute neutrophil count to > or = 1,500/microliter and/or platelets to > or = 100,000/microliter by day 28; and any grade > or = 3 nonhematologic toxicity. Two MTDs were defined: the first without granulocyte colony-stimulating factor (MTD 1) and the second with granulocyte colony-stimulating factor given either to accelerate recovery of grade 4 neutropenia lasting more than 72 hours or immediately in case of febrile neutropenia (MTD 2); granulocyte colony-stimulating factor was never used prophylactically. To date, 22 patients have been entered into the study; the median patient age was 55 years (age range, 30 to 66 years). Nineteen (86%) patients had received adjuvant chemotherapy that included anthracyclines in 12 cases (55%). The viscera were the dominant sites of disease in 55% of patients. Median baseline ventricular ejection fraction was 58% (range, 53% to 67%). Short-lasting grade 4 neutropenia occurred in 61% of courses; however, only four episodes of febrile neutropenia were recorded. Grade 4 thrombocytopenia was reported in 8% and grade 3 anemia in 3% of courses; four patients experienced peripheral neuropathy (three patients grade 1, one patient grade 2); complete alopecia was universal. The cardiac effects of the combination were surprisingly low: median ejection fraction at study entry was 58%, and after a cumulative dose 1,080 mg/m2 it was 56%. Three complete responses and 12 partial responses have been documented for an overall response rate of 83.3% (95% confidence interval, 58% to 96%). In conclusion, neutropenia is the most frequent toxicity of this novel combination. However, the MTD has not yet been reached. The combination of epirubicin plus paclitaxel is highly active, and no signs of cumulative myocardiopathy have been observed.

Adult↗
PubMed1996

A dose-finding study of epirubicin in combination with paclitaxel in the treatment of advanced breast cancer.

We performed a dose escalation study to evaluate the maximum tolerated dose of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) given over 3 hours plus bolus epirubicin 90 mg/m2. The starting dose of paclitaxel, 135 mg/m2, was escalated by 20-mg/m2 increments in cohorts of three to six patients. Courses were repeated every 3 weeks. Filgrastim (5 micrograms/kg/d) was administered to shorten the duration of grade 4 neutropenia lasting longer than 72 hours. Twenty-nine patients have been treated, 86% of whom had failed adjuvant chemotherapy (with anthracyclines in 14 cases). One hundred forty-eight courses have been administered, and the paclitaxel dose has been escalated to 225 mg/m2 without reaching the maximum tolerated dose. The most frequent dose-related toxicity has been grade 4 neutropenia, which occurred in 59% of courses. The median duration of grade 4 neutropenia was 4 days, which was shortened with filgrastim only in patients treated with paclitaxel 225 mg/m2. Eleven episodes of febrile neutropenia (7% of courses) have been observed. Nonhematologic toxicities were mild or moderate: grade 1 or 2 peripheral neuropathy was reported by 41% and 10% of patients, respectively. The cardiac toxicities of this regimen were surprisingly low: median left ventricular ejection fraction was 57% at study entry and 56% after six courses. Only two patients showed a decrease of left ventricular ejection fraction below 50% after six courses, and no signs of anthracycline-induced congestive heart failure were noted. The activity of this novel combination is encouraging: the overall response rate is 80%, with 16% complete responses. We have demonstrated that the combination of epirubicin plus paclitaxel given over 3 hours is feasible with acceptable toxicities, does not appear to be associated with clinically relevant cardiotoxicity, and is active in a population of patients who have failed adjuvant chemotherapy.

Adult↗