Search PubMed⌕ Search

Biomedical subjects

G Bonadonna

Publications and source records attributed to G Bonadonna.

At least 37 records · Page 2Linked to original sources
PubMed2000

Gemcitabine in the treatment of refractory Hodgkin's disease: results of a multicenter phase II study.

PURPOSE: To explore the use of gemcitabine for the treatment of patients with relapsing or refractory Hodgkin's disease. PATIENTS AND METHODS: Eligible patients had measurable disease and more than one previous chemotherapy regimen. Patients previously treated with high-dose chemotherapy with autologous bone marrow or peripheral stem-cell support were not included. Gemcitabine, 1,250 mg/m(2), was administered as a 30-minute intravenous infusion on days 1, 8, and 15 of each 28-day cycle of therapy. The dosing schedule remained fixed, and any dose of gemcitabine that could not be given on time was omitted. Patients who had not experienced any hematologic or nonhematologic toxicity after one complete cycle of therapy were permitted to have subsequent doses increased by 20%: that is, from 1, 250 mg/m(2) to 1,500 mg/m(2). RESULTS: Of the 23 enrolled patients, 22 were assessable for response; all 23 patients were included in the efficacy analysis. Disease status for two patients (9%) reached a state of complete remission, and seven patients (30%) achieved a partial response, for an overall response rate of 39% (95% confidence interval, 19.7% to 61.5%). The likelihood of achieving a response was not influenced by a patients' main pretreatment characteristics or by their response to their last prior chemotherapy. The median duration of response was 6.7 months (range, 2 to 33+ months), and the median overall survival time was 10.7 months (range, 4 to 34.7+ months). In general, toxicities were mild; no treatment-related deaths occurred, and only one life-threatening adverse event was reported for this study. CONCLUSION: Gemcitabine was shown to be active in heavily pretreated patients with Hodgkin's disease, producing a response rate of 39%. Additionally, drug-related toxicities were mild, which thus suggests the possible inclusion of gemcitabine in an earlier phase of treatment.

Adult↗
PubMed1999

Comparative analysis of breast cancer recurrence risk for patients receiving or not receiving adjuvant cyclophosphamide, methotrexate, fluorouracil (CMF). Data supporting the occurrence of 'cures'.

PURPOSE: To comparatively analyse the risk of recurrence at given times after surgery for breast cancer patients receiving or not receiving adjuvant CMF. PATIENTS AND METHODS: A total of 1452 node positive patients, who entered controlled clinical trials carried out at the Milan Cancer Institute and underwent radical or modified radical mastectomy for operable breast cancer, were examined. In 575 cases no further treatment was performed, whereas 877 pts were given 6 or 12 courses of adjuvant Cyclophosphamide, Methotrexate, Fluorouracil (CMF). The recurrence risk was estimated by the event-specific hazard rate for first failure and distant metastases, and, following Efron, hazard rates were fitted by logistic regression models. RESULTS: The hazard rate for first failure and distant metastases showed a double peaked pattern for both treated patients and controls, with a first major peak at about 18-24 months from surgery (early metastases), a second minor peak at the 5th-6th year, and a tapered plateau-like tail extending over 10 years from surgery (late metastases). As expected, the recurrence risk of CMF treated patients was lower than the corresponding risk of patients undergoing surgery only. However, the difference was highly evident for early recurrences, while it declined and disappeared afterwards. CONCLUSION: Our findings confirm previous reports on patients not receiving adjuvant chemotherapy, suggesting that the recurrence risk for operable breast cancer has a multipeak pattern. As far as CMF treated patients are concerned, the unchanged peak timing together with the early recurrence risk reduction in comparison to controls are much more consistent with the real nonappearance of some early recurrences (putatively 'cured' patients) than with the delay in their manifestation. As late relapsing patients seem to have at most marginal benefits from adjuvant CMF, ways to recognize patients doomed to have late recurrence and new ways for treating micrometastases resulting in late recurrences are required.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

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.

Adult↗
PubMed1999

Gemcitabine as a single agent in the treatment of relapsed or refractory aggressive non-Hodgkin's lymphoma.

PURPOSE: A multicenter phase II trial was conducted to evaluate the efficacy and toxicity of gemcitabine in patients with relapsed or refractory aggressive non-Hodgkin's lymphomas (NHL). PATIENTS AND METHODS: Thirty-one patients with B-cell intermediate or high-grade NHL (Working Formulation) were enrolled onto the study. The median age was 61 years, with a Karnofsky performance status of </= 80% in 65% of patients. Forty-eight percent had stage III or IV (Ann Arbor Classification) at study entry. Pretreatment consisted of one, two, or three chemotherapeutic regimens in nine, 11, and 11 patients, respectively. Gemcitabine 1,250 mg/m(2) was administered intravenously over 30 minutes on days 1, 8, and 15 of a 28-day schedule. RESULTS: Thirty patients were assessable for efficacy, and 31 were assessable for toxicity. No complete responses were observed, but six patients showed a partial response, 11 stable disease, and 13 progressive disease. The overall response rate was 20% (95% confidence interval, 8% to 39%) for assessable patients and 19% (95% confidence interval, 8% to 34%) for the intent-to-treat analysis. The median duration of partial response was 6 months (range, 3.7 to 15+ months). Nonhematologic World Health Organization grade 3 toxicity included hepatic toxicity in four patients and infection in two. Hematologic toxicity was observed as grade 3 anemia in three patients, grade 3 leukopenia in two patients, grade 3/4 neutropenia in two patients, and grade 3/4 thrombocytopenia in six patients. CONCLUSION: The present schedule of gemcitabine displays modest efficacy and mild toxicity in pretreated aggressive NHL.

Adult↗
PubMed1999

Diffuse large-cell lymphoma of the testis.

PURPOSE: To evaluate clinical outcome of patients with testicular diffuse large-cell lymphoma treated with conventional-dose systemic chemotherapy. PATIENTS AND METHODS: This study is a retrospective analysis of adult patients with testicular diffuse large-cell lymphoma who were treated with a doxorubicin-based chemotherapy regimen at our institution, the Istituto Nazionale Tumori of Milan. Twenty-nine assessable patients, with a median age of 61 years, were identified. Sixteen patients had limited stage (Ann Arbor stage I/II) disease, whereas 13 patients had a testicular mass and distant organ involvement (Ann Arbor stage IV). Patients were retrospectively classified according to the International Prognostic Index. RESULTS: After a median follow-up of 82 months, 22 patients presented disease progression and 22 patients had died. Actuarial median time to treatment failure and overall survival were 44 and 41 months for patients with limited stage and 9 and 16 months for patients with advanced stage, respectively. Eight patients failed initial treatment, and 14 patients relapsed from clinical remission after a median disease-free time of 17 months (range, 6 to 98 months). Median survival time after progression of lymphoma was 5 months (range, 0 to 22 months). In nine (41%) of the 22 failing patients, the initial site of relapse was either the CNS or the contralateral testis; the remaining patients experienced relapse in multiple extranodal sites. CONCLUSION: Poor prognosis of patients with diffuse large-cell lymphoma calls for more effective treatment strategies, such as high-dose chemotherapy programs for younger patients or specifically designed chemotherapy regimens for patients not suitable for high-dose treatment, with the purpose to provide control of both systemic disease and disease of the CNS and contralateral testis. The potential benefit of contralateral testicular irradiation has to be taken into account in the treatment planning.

Adult↗
PubMed1998

Putting taxanes to work in operable breast cancer: a search for selective indications from empirical studies.

The taxanes paclitaxel and docetaxel are the prototype drugs of a new class of anticancer drugs that exploits a completely new mechanism of action. Their testing in metastatic breast cancer has been extensive. The results indicating very high response rate with either taxane have given rise to an unprecedented effort in the scientific community to define their optimal application in all stages of the disease. In metastatic breast cancer, initial data suggest that paclitaxel may increase the survival obtained with standard combinations such as CMFP, and similarly promising studies of docetaxel are almost complete. Significant therapeutic benefit has also been observed by the addition of sequential paclitaxel after adjuvant doxorubicin plus cyclophosphamide in operable breast cancer. Overall, more than 20 randomized studies with paclitaxel or docetaxel, either as single agents or in combination, are ongoing or planned in women with high-risk operable breast cancer. This massive effort is mainly based on empirical study designs. However, some preclinical characteristics of the taxanes, such as their increased antitumor effect in tumors overexpressing HER2/neu, the preclinical and clinical evidence of potential synergism with monoclonal antibodies directed against the HER2 receptor, and preclinical evidence of antiangiogenic properties should be pursued to test whether the use of taxanes in breast cancer could be tailored to individual tumor characteristics rather than following the usual pattern of indiscriminate application.

Breast Neoplasms↗
PubMed1998

Estimate of tumor growth time for breast cancer local recurrences: rapid growth after wake-up?

To obtain an estimate of the subclinical tumor growth time (TGT) for breast cancer, a series of 31 patients with local recurrence as first event after mastectomy was evaluated. The recurrence diameter was measured, and the minimum growth rate (mGR) consistent with the sequence 'no detection at the preceding physical examination-->recurrence of diameter Dr' was obtained. The growth rate for uninterrupted exponential growth from surgery (GRu) was also calculated. mGR was significantly higher than GRu (p < 0.0001), and unrelated to the recurrence-free survival (RFS). Therefore, starting points of local recurrence growth curves had to be set at times variously delayed after mastectomy. The estimate of the delay lower limit (mD), which was obtained from mGR and GRu, showed a strong linear correlation with RFS (R = 0.984; p < 0.0001). From the regression equation, TGT for local recurrences could be estimated at 30+/-8 weeks or less. These findings support the concept that the lag time between surgical treatment of breast cancer and clinical evidence of local recurrence may be explained by a period of tumor dormancy followed by a tumor growing phase. The TGT estimate is remarkably shorter than previously believed and could considerably change the current picture of breast cancer history.

Adult↗
PubMed1998

Soluble interleukin-2 receptors (sIL-2R) in Hodgkin's disease: outcome and clinical implications.

The aim of this study was to assess the prognostic role of soluble interleukin-2 receptors (sIL-2R) in Hodgkin's disease (HD) both in the achievement of complete remission (CR) and in predicting disease relapse. Between August 1988 and June 1993 sIL-2R serum levels were measured in 174 untreated patients; in 137 of them evaluation was repeated at the end of treatment and in 132 also during the follow-up. Baseline sIL-2R levels (mean+/-standard error) were significantly higher in patients than in 65 healthy control subjects (1842+/-129 U ml(-1) vs 420+/-10 U ml(-10, P< 0.0001). At the end of treatment 135 out of 137 evaluated patients achieved complete response (CR) and their mean sIL-2R serum levels were significantly lower than those at diagnosis (635+/-19 U ml(-1) vs 1795+/-122 U ml(-1), P=0.0001). After a median follow-up of 5 years, sIL-2R remained low in 114 patients in continuous CR, while they increased in 9 out of 12 patients (75%) who relapsed. However, a temporary increase was also observed in six patients (5%) still in CR. Treatment outcome in terms of freedom from progression was linearly related to sIL-2R levels. Our study confirms that patients with untreated HD have increased baseline levels of sIL-2R compared with healthy subjects and that their pretreatment values may be an indication of disease outcome similar to other conventional prognostic factors, such as number of involved sites, presence of B symptoms and extranodal extent.

Adolescent↗
PubMed1998

Ifosfamide and vinorelbine: an active regimen for patients with relapsed or refractory Hodgkin's disease.

Twenty-six patients with relapsed or refractory Hodgkin's disease (HD) were treated with an intensive salvage regimen combining ifosfamide (3000 mg/m2/d, days 1-4 through continuous intravenous infusion) and vinorelbine (25 mg/m2, i.v. days 1 and 5) with mesna uroprotection and G-CSF support. Courses were given at 3-week intervals. Ten patients achieved a complete and 10 patients a partial response, yielding an overall response rate of 77%. The main toxic effect was neutropenia and the combination was well tolerated.

Adult↗
PubMed1998

Primary chemotherapy in operable breast cancer: eight-year experience at the Milan Cancer Institute.

PURPOSE: Primary chemotherapy was administered to patients with tumors that measured > or = 2.5 cm in largest diameter to decrease the size of the primary tumor and allow for effective local and distant control while avoiding mastectomy. PATIENTS AND METHODS: Two prospective nonrandomized studies were performed that used different regimens of primary chemotherapy followed by breast-sparing surgery in the presence of objective tumor remission. Additional postoperative chemotherapy was given to women at high risk of disease relapse. The median follow-up duration was 65 months. RESULTS: A total of 536 assessable patients were enrolled, and the main characteristics were fairly comparable between the two trials. Following primary chemotherapy, 85% of patients could be subjected to breast-sparing surgery; in 14 patients (3%), surgical specimens failed to show any residual neoplastic cell. In the final multivariate analysis, the histologically assessed extent of axillary node involvement (P < .001), as well as degree of response to primary chemotherapy (P = .034), represented the significant variables able to influence 8-year relapse-free survival. In women subjected to a breast-conserving approach, the cumulative risk of local relapse as first event alone was 6.8% (95% confidence interval, 3.9% to 8.8%). CONCLUSION: Current findings indicate that primary chemotherapy can be safely administered in women with large tumors (>5.0 cm) and can allow breast-sparing surgery in a high fraction of patients (62%). However, to assess effectively the worthiness of this approach on long-term results, properlyconceived large randomized studies with newer and more effective drug regimens are warranted.

Adult↗
PubMed1998

End points in the analysis of breast cancer survival: relapse versus death from tumor.

BACKGROUND: To determine whether relapse and death from tumor are comparable as survival end points for assessing therapeutic efficacy, five prospective, randomized clinical trials of adjuvant therapy for stage II breast cancer were analyzed. One thousand eight hundred ninety patients were combined from five clinical groups into a single group for analysis. METHODS: Actuarial and parametric survival methods were used to generate three estimates for the likelihood of cure (LOC): (1) for all patients, with relapse as the end point to survival (LOCR); (2) for all patients, with death from tumor as the end point (LOCD); and (3) for patients with relapse only with death from tumor as the end point (LOCRD). Linear regression analysis was used to compare time to relapse for each patient with time from relapse to death. RESULTS: Estimates of LOCR ranged from 33.5% to 38.4%, estimates of LOCD ranged from 36.3% to 44.2%, and estimates of LOCRD ranged from 0% to 6%. Thus LOCR and LOCD are approximately equal for these patients. On the other hand, time to relapse correlated poorly with time from relapse to death (r2 = 0.005). CONCLUSIONS: If therapy affects LOC, relapse and death should ultimately lead to the same conclusion with respect to therapeutic efficacy, because both end points lead to essentially the same LOC. If therapy affects time to relapse, however, these two end points may ultimately lead to different conclusions, because time to relapse correlates poorly with time from relapse to death.

Actuarial Analysis↗
PubMed1997

High-dose chemotherapy and autologous bone marrow transplantation compared with MACOP-B in aggressive B-cell lymphoma.

BACKGROUND: We compared a regimen of six chemotherapeutic agents administered sequentially at high doses, followed by myeloablative treatment and bone marrow transplantation, with a regimen of methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B) as initial or salvage treatment for adults with diffuse large-cell lymphoma. METHODS: Ninety-eight eligible patients with diffuse large-cell lymphoma of the B-cell type were randomly assigned to receive either MACOP-B (50 patients) or high-dose sequential therapy (48 patients). The study design allowed for patients in whom the assigned treatment failed to cross over to the other treatment group. RESULTS: After a median follow-up of 55 months, the patients given high-dose sequential therapy, as compared with those treated with MACOP-B, had significantly higher rates of complete response (96 percent vs. 70 percent, P=0.001), freedom from disease progression (84 percent vs. 49 percent, P<0.001), freedom from relapse (88 percent vs. 70 percent, P=0.055), and event-free survival (76 percent vs. 49 percent, P=0.004). The difference in overall survival at seven years, which also favored the group assigned to high-dose sequential therapy, was marginally significant (81 percent vs. 55 percent, P=0.09). CONCLUSIONS: High-dose sequential therapy is superior to standard-dose MACOP-B for patients with diffuse large-cell lymphoma of the B-cell type.

Adolescent↗
PubMed1997

Five-day infusion fluorouracil plus vinorelbine i.v. in metastatic pretreated breast cancer patients.

The aim of the present study was to evaluate the clinical activity and side effects of a combination chemotherapy consisting of a five-day continuous infusion of fluorouracil and i.v. vinorelbine in metastatic previously treated breast cancer patients. The patient population was represented by 28 women with evaluable disease, previously subjected to chemotherapy, including anthracycline-containing regimens in 89% of patients. Treatment consisted of five-day infusion of 700 mg/m2/day of fluorouracil and vinorelbine, 20 mg/m2 i.v. bolus on day 1 and 6. In the absence of Grade > 3 leukopenia and stomatitis, cycles were repeated every three weeks, for a total of six cycles. Four complete and thirteen partial responses were documented, accounting for a response rate of 61% (95% CI: 40.5-78.5); the clinical efficacy was high even in patients unresponsive to prior anthracycline treatment. The median response duration calculated from the first drug injection was 8 months (range 4-11). Treatment was well tolerated, with 4% Grade 4 stomatitis and 20% Grade 3 leukopenia as the main toxic reactions. This drug combination is active in metastatic previously treated breast cancer patients, is devoid of severe side effects, and warrants further testing.

Adult↗
PubMed1997

Computer simulation of a breast cancer metastasis model.

Recent analysis of relapse data from 1173 untreated early stage breast cancer patients with 16-20 year follow-up shows that frequency of relapse has a double peaked distribution. There is a sharp peak at 18 months, a nadir at 50 months and a broad peak at 60 months. Patients with larger tumors more frequently relapse in the first peak while those with smaller tumors relapse equally in both peaks. No existing theory of tumor growth predicts this effect. To help understand this phenomenon, a model of metastatic growth has been proposed consisting of three distinct phases: a single cell, an avascular growth, and a vascularized lesion. Computer simulation of this model shows that the second relapse peak can be explained by a steady stochastic progression from one phase to the next phase. However, to account for the first relapse peak, a sudden perturbation of the development at the time of surgery is necessary. Model simulations predict that patients who relapse in the second peak would have micrometastases in states of relatively low chemosensitivity when adjuvant therapy is normally administered. The simulation predicts that 15% of T1, 39% of T2, and 51% of T3 staged patients benefit from adjuvant chemotherapy, partially offsetting the advantage of early detection. This suggests that early detection and adjuvant chemotherapy may not be symbiotic strategies. New therapies are needed to benefit patients who would relapse in the second peak.

Breast Neoplasms↗
PubMed1997

Initial chemotherapy for primary resectable large-cell lymphoma of the stomach.

BACKGROUND: We aimed to evaluate the safety and effectiveness of a conservative approach with short-term chemotherapy with or without consolidation radiotherapy in primary resectable large-cell gastric lymphoma in patients not requiring emergency surgery at presentation. PATIENTS AND METHODS: Seventeen consecutive patients presenting with resectable primary large-cell lymphoma of the stomach not requiring immediate surgery were initially treated with chemotherapy with or without consolidation radiotherapy. Subtotal or total resection of the stomach was planned only as salvage treatment for those patients who failed locally, or as emergency surgery in instances of acute iatrogenic complications of treatment. Chemotherapy included four to six cycles of an anthracycline-containing regimen, and consolidation radiotherapy was planned on the entire stomach and surrounding lymph node areas for complete responders readily capable of compliance with a daily treatment schedule at our Institution. RESULTS: None of the patients in the present series experienced acute iatrogenic morbidity or mortality from local complications. After a median follow-up of almost six years, two patients failing first-line chemotherapy have died of progressive lymphoma, while 15 patients are well and currently disease-free. CONCLUSIONS: Up-front chemotherapy as initial treatment for primary gastric large-cell lymphoma appears to be a safe and effective treatment by which most patients can probably be spared surgical gastrectomy. Consolidation radiation therapy on the stomach can probably improve on the effectiveness of chemotherapy alone. More experience is needed to elucidate the prognostic factors, treatment-related long-term toxic effects and the feasibility of such a treatment administered outside of highly specialized institutions.

Adult↗
PubMed1997

Proposal for a new model of breast cancer metastatic development.

BACKGROUND: The commonly accepted theory of breast cancer metastatic development assumes continuous tumor growth from tumor seeding until documentation of clinical recurrence. In particular, Gompertzian growth kinetics is currently the theoretical cornerstone of the natural history of breast cancer, and has been widely utilized for planning treatments. MATERIALS AND METHODS: To verify agreement between findings and the implications of the continuous growth model, several published papers about the natural history of breast cancer after removal of the primary tumor were reviewed. Also, findings from animal models concerning metastasis biology were considered. RESULTS: The continuous growth model failed in important ways upon this critical reappraisal. As an alternative, the tumor dormancy hypothesis was considered to provide a more reasonable description of tumor recurrence. Moreover, primary tumor removal was revealed as a potentially perturbing factor for metastasis development. CONCLUSIONS: A new general outline of metastatic development of breast cancer incorporating tumor dormancy in specific micrometastatic phases, stochastic transitions between them, and start signals from surgery for micrometastatic growth was designed. The proposed model suggests new views concerning scheduling of current chemotherapy, new treatment approaches aimed at keeping micrometastases in a dormant state for the patient's entire life, and the careful reappraisal of the timing of surgery within the multimodal treatment of operable breast cancer.

Breast Neoplasms↗