Pinuccia Valagussa

Comparison of different trials of adjuvant chemotherapy in stage II breast cancer using a natural history data base.

Prognostic factors and treatment were analyzed for 2,578 patients to assess the impact of various forms of adjuvant chemotherapy on the natural history of operable stage II (node-positive) breast cancer. The outcome after surgery alone (or with radiotherapy) was determined in 1,014 patients in the natural history data base (NHDB). Adjuvant chemotherapy consisted of L-phenylalanine mustard (L-PAM; 130 patients); cyclophosphamide, methotrexate, and 5-fluoro-uracil (CMF; 645 patients); doxorubicin and cyclophosphamide (AC; 241 patients); CMF plus vincristine and prednisone (CMFVP; 263 patients); and 5-fluorouracil plus AC (FAC; 285 patients). L-PAM had minimal effect on relapse-free survival (RFS) compared to the NHDB, but all combination chemotherapy programs significantly improved RFS and survival compared to the NHDB. In women with 1–3 positive nodes, all combination chemotherapy programs produced similar results. In women with 4–9 positive nodes, the FAC regimen appeared to be associated with superior RFS compared to other programs, but all were superior to the NHDB. In women with 10 or more positive nodes, FAC was the only regimen associated with improved RFS. The use of a NHDB and known pretreatment characteristics, such as nodal status and tumor size, permits comparison of patients at similar risk of recurrence of breast cancer who have received adjuvant chemotherapy and provides leads for evaluation in future prospective clinical trials.

Development and use of a natural history data base of breast cancer studies

Pretreatment information, type of treatment, and longitudinal follow-up on 1,971 patients with operable breast cancer were used to establish a breast cancer natural history data base (NHDB). Data were available for 957 patients with stage I (node-negative) breast cancer and 1,014 stage II (node-positive) patients. In women with negative nodes, information was available on 759 patients treated at the Milan National Cancer Institute and 188 patients treated at the Royal Marsden Hospital. After adjustment for differences in the distribution of patient prognostic factors, relapse-free survival and overall survival were not significantly different. Of the 1,014 node-positive patients, 540 were treated at the Milan National Cancer Institute, 258 at the Royal Marsden, and 216 at the M. D. Anderson Hospital. Relapse-free survival and overall survival did not significantly differ between Milan patients and those treated at the Royal Marsden Hospital. However, M. D. Anderson Hospital patients did have significantly better relapse-free and overall survival. In each institution, outcome was consistently most dependent on the number of involved axillary lymph nodes and tumor size. Also, similar patterns of survival were observed for each of the institutions. The development of an NHDB can be of value in the identification and evaluation of consistency of prognostic factors, permitting improved comparisons between clinical trials. The development of such a natural history data base (NHDB) provides a reference for assessing the impact of different adjuvant chemotherapy programs, and aids in the design of new protocols.

Elevated pretreatment serum levels of Il-10 are associated with a poor prognosis in hodgkin's disease, the Milan Cancer Institute Experience

Alterated cytokine secretion may play a role in determining Hodgkins disease-related immunosuppression. The aim of this study was to analyze the clinical significance of interleukin-10(IL-10) serum levels in 73 chemotherapy-naive patients with Hodgkins disease. We evaluated the relationship between pretreatment circulating values of IL-10 and both the clinical characteristics of the disease as well as the prognosis in terms ofreedom from progression and overall survival. Abnormally high pre-treatment serum levels (mean±standard error: 26.79±13.24 pg/ml) were detected in 33/73 (45%) patients. The percentage of patients with enhanced IL-10 secretion was significantly higher in the presence of advanced disease (56% vs 32%,P<0.03), systemic symptoms (57%vs 34%,P<0.04) and more than 3 involved sites (61%vs 36%,P<0.03).The high basal levels of IL-10 negatively influenced long-term results: at 8-years freedom from progression (FFP) and overall survival (OS) for patients with IL-10>6 pg/mlvs≤6 pg/ml were 69% and 76%vs 97.5% and 95%, respectively. The multivariate analysis confirmed the prognostic value of IL-10 basal serum levels (FFP,P=0.0001; OS,P=0.06). Our study suggests that high pre-treatment circulating levels of IL-10 are associated with a poor prognosis, irrespective of other common prognostic variables.

Textbook of breast cancer : a clinical guide to therapy

Epidemiology and screening pathology prognostic factors genetic counselling current role of surgeon in collaborating with medical oncologists primary chemotherapy conventional adjuvant chemotherapy conventional adjuvant hormonal therapy locally advanced breast cancer routine management of disseminated disease salvage therapy after adjuvant systemic therapy radiotherapy plus chemotherapy - concomitant or subsequent delivery long-term side effects from systemic drug therapy supportive therapy new chemotherapy drugs new hormones role of high-dose chemotherapy current role of growth factors in the management of breast cancer chemoprevention routine treatment vs controlled trials.

Combined sequential approach in locally advanced breast cancer

BACKGROUND The interaction between primary and adjuvant chemotherapy is a crucial point in the treatment of locally advanced breast cancer. OBJECTIVE To evaluate the therapeutic efficacy of a sequential treatment with primary anthracyclines and adjuvant CMF in this patient subset. DESIGN Prospective cohort study. PATIENTS Eighty-eight breast cancer patients, stage T3b-T4 abc, N0-2, M0. RESULTS From February 1991 to July 1994, 88 consecutive patients with locally advanced breast cancer were treated at the Istituto Nazionale Tumori, Milano, with full-dose doxorubicin (75 mg/m2) or epirubicin (120 mg/m2) for three cycles followed by surgery, adjuvant chemotherapy with i.v. CMF for six cycles and local radiotherapy +/- Tamoxifen. A high rate of objective responses (70%), but a low incidence of pathologic complete remission (2%), were observed following primary treatment with single-agent anthracyclines. Frequency of responses was not associated with tumor estrogen or progesterone receptors status, Mib-1 or grading. In 28 patients (32%) conservative surgery could be performed. At a median follow-up of 52 months, relapse free survival and overall survival are 52% and 62%, respectively. A multivariate analysis demonstrated a significant favorable prognosis in patients with limited nodal involvement at surgery and negative Mib-1 values. This drug sequence failed to significantly ameliorate the long term results in this unfavorable patient subset and more effective drug regimens and innovative therapeutic strategies are needed.

Mitoxantrone: an active agent in refractory non-Hodgkin's lymphomas

A phase II oriented study with mitoxantrone was undertaken in 31 patients with refractory non-Hodgkins lymphomas (NHL); 30 patients had evaluable disease. The drug was administered through a 30-min intravenous infusion at the dose of 14 mg/m2 every 3 weeks. A minimum of two cycles were required to define treatment response. Twenty patients were previously treated with Adriamycin whose total dose was not exceeding 300 mg/m2. Complete response (CR) was documented in 9 patients, and partial response (PR), in 5 for a total response rate of 47% (14 of 30). Of 20 patients previously treated with Adriamycin, CR occurred in five and PR in two. The median time to progression was 3 months. Mitoxantrone was well tolerated, and no patient refused treatment. Mild leukopenia was evident in 10 patients and thrombocytopenia in 5 patients. In all cases, electrocardiograms (EKGs) was obtained before each treatment cycle. Systolic time intervals and left ventricular ejection fraction were repeated after 3 cycles and at the end of therapy. Laboratory tests failed to document any major cardiac abnormality. Mitoxantrone is an effective agent in refractory NHL and should be taken into consideration in the design of salvage regimens.

Intermediate doses of cyclophosphamide alone or following adriamycin in advanced breast cancer : a pilot study

Cyclophosphamide (CTX) is an active drug in breast cancer and presents a well-established dose-response relationship. To explore further this relationship, the present pilot study investigated the therapeutic efficacy of cyclophosphamide at intermediate dose in two groups of untreated patients with advanced breast cancer. Nine women received the drug alone at 3-4 g/m2 i.v. every 2 weeks for a total of three doses. The same dose schedule was also given to 11 women following the administration of four cycles of Adriamycin, at 75 mg/m2 i.v. every 3 weeks. We documented one partial remission in untreated women and four partial responses in Adriamycin-treated patients. The major toxicity was represented by leukopenia and neutropenia. Myelosuppression was relevant but of short duration, and the use of G-CSF appeared useful in controlling this side effect. In spite of the high dose intensity of the present cyclophosphamide dose schedule (9 g/m2 in 4 weeks), i.e., almost three times superior to that conventionally employed, present results do not suggest its superiority over the current chemotherapeutic regimens utilized in advanced disease.