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P Valagussa

Publications and source records attributed to P Valagussa.

At least 73 records · Page 4Linked to original sources
PubMed1994

Cardiac effects following adjuvant chemotherapy and breast irradiation in operable breast cancer.

AIM: To assess the frequency and type of cardiac effects in women treated with adjuvant chemotherapy with or without breast irradiation for operable breast cancer. PATIENTS AND METHODS: Retrospective analysis of a series of 825 women taking part in prospectively randomized trials on adjuvant chemotherapy with or without adriamycin (doxorubicin; Farmitalia-Carlo Erba, Milan, Italy) for operable breast cancer at high risk of new disease manifestations. A total of 360 patients (44%) also received breast irradiation because of conservative surgery. Median follow-up in first clinical complete remission from end of all adjuvant treatments was 80 months. According to the protocol requirements, electrocardiograms were obtained before breast cancer surgery, before starting therapy with adriamycin and at the end of all adjuvant treatments. During the follow-up observation, electrocardiograms were systematically obtained at least once a year. In the presence of suspicious findings as well as of clinical symptoms and signs of cardiovascular disease, additional cardiac investigations were undertaken. However, percutaneous endomyocardial biopsies were never performed. RESULTS: Congestive heart failure occurred in a total of 4 women (0.5% of all patients; 0.8% following adriamycin-containing chemotherapy; 2.6% after both adriamycin and irradiation to the left breast), in two of whom it was fatal. ST-segment and T-wave abnormalities in the absence of other symptoms and signs were detected in 3.4% of the case series. Other cardiac events were documented in 6.8% of all patients Overall, cardiac effects were more frequently detected in women who received irradiation to the left breast. In addition, age greater than 55 years at surgery and history of risk factors were important risk modifiers in the occurrence of cardiac events. CONCLUSIONS: The addition of full-dose adriamycin to alkylating-containing adjuvant chemotherapy, as given in our studies, failed per se to increase the frequency of cardiac effects. Thus anthracyclines, which have the potential to improve current treatment results, deserve a proper place in the design of future adjuvant studies.

Adult↗
PubMed1994

Second malignancies following CMF-based adjuvant chemotherapy in resectable breast cancer.

BACKGROUND: Only a few studies have evaluated the long-term effects of adjuvant chemotherapy for breast cancer. Furthermore, neither the relation between the risk of second malignancies and type of adjuvant regimen utilized nor the interaction between chemotherapy and breast irradiation or age of the patients have been described in detail. METHODS: A total of 2,465 patients entered into prospective studies of CMF-based adjuvant chemotherapy carried out at the Milan Cancer Institute between June 1973 and July 1990 were evaluated. The median follow-up was 12.0 years and detailed information about therapy was available for all patients. RESULTS: At 15 years, the cumulative actuarial risk of second malignancies (excluding contralateral breast cancer and basal skin cancer) was 6.7% +/- 0.8% for the total series. The figures were 8.4% +/- 2.9% after local-regional treatment alone, 6.4% +/- 0.9% following CMF, and 5.1% +/- 1.0% following CMF plus Adriamycin (doxorubicin; Farmitalia-Carlo Erba, Milan, Italy). Compared to the general female population, the relative risk following CMF-based adjuvant chemotherapy was 1.29. Three patients, all of whom had received CMF-based chemotherapy, developed acute non-lymphocytic leukemia (cumulative risk 0.23% +/- 0.15%; relative risk 2.3). No differences were evident when breast irradiation was considered, but the cumulative risk of second tumors was slightly higher in women aged > or = 50 years at surgery (7.7% +/- 1.3%) than in younger patients (6.0% +/- 1.0%). CONCLUSIONS: At present, there is no evidence of a significantly increased risk of second malignancies following adjuvant CMF-based chemotherapy such as the one given in this case series. A low risk of acute leukemia was associated with the cumulative total dose of cyclophosphamide administered, and breast irradiation did not enhance this risk. IMPLICATIONS: Our findings suggest that there is no reason to omit alkylating agents from short-term effective adjuvant chemotherapy.

Actuarial Analysis↗
PubMed1994

Vinorelbine: an active drug for the management of patients with heavily pretreated Hodgkin's disease.

BACKGROUND: This study evaluated the therapeutic effect of the weekly administration of vinorelbine (5'-nor-anhydrovinblastine), a semisynthetic vinca alkaloid, in heavily pretreated patients with Hodgkin's disease. PATIENTS AND METHODS: Twenty-four patients with Hodgkin's disease refractory or resistant to at least two chemotherapy regimens were enrolled in this study. Vinorelbine was administered in a weekly dose of 30 mg/m2 i.v. bolus and patients were evaluated after four courses. All but two were considered evaluable for drug response. The reasons for their exclusion were early death due to pancytopenia and loss to follow-up after two courses. In complete responders, six additional courses were administered; in all other patients, treatment was continued until their diseases progressed. Toxicity was evaluated in 23 patients according to the Common Toxicity Criteria. RESULTS: Eleven of 22 evaluable patients (50%) showed objective response (complete 14% and partial 36%). The median duration of response was six months for both complete and partial responders (range 2-10 months). Thirteen patients are still alive and five are still on therapy. Grade 3-4 granulocytopenia was documented in 53% of patients and grade 3 infections in 13%. Anemia and thrombocytopenia were negligible. Nausea and vomiting were not observed; grade 2 alopecia occurred in only one patient. There were grade 3 reactions at the injection site in the first five patients, so a venous central access was utilized in the subsequent patients. Two patients had grade 1 constipation and only one developed an adynamic ileum. Although all patients had previously been treated with vinca alkaloid analogs, peripheral neuropathy was mild. CONCLUSIONS: Our data indicate that vinorelbine is active as a single agent in heavily pretreated patients with Hodgkin's disease. The efficacy in patients pretreated with at least two vinca alkaloids suggests a possible absence of cross-resistance between vinorelbine and other vinka analogs. Toxicity is mild and reversible. The inclusion of vinorelbine in secondline combination chemotherapy regimens for Hodgkin's disease is strongly recommended.

Antineoplastic Agents↗
PubMed1993

Combined modality treatment for primary gastrointestinal non-Hodgkin's lymphoma: the Milan Cancer Institute experience.

BACKGROUND: The study analyzes clinical-pathologic features, treatment and outcome of all patients with primary lymphoma of the gastrointestinal tract (GI-NHL) seen during the past two decades at the Milan Cancer Institute. SUBJECTS AND METHODS: Clinical and histopathological data from 135 patients presenting with GI-NHL and disease localized within the abdomen were reviewed. Of these, 114 (84%) presented with limited disease (stage I and II), while 21 patients were found to have disease involvement of other abdominal organs (i.e., liver, pancreas, peritoneum) or more than one gastrointestinal site and were therefore classified as stage IV. Seventy-three percent presented with lymphoma in the stomach, 15% in the small intestine and 9% in the large bowel, while in 5 cases multiple localizations of the gastrointestinal tract were documented. Median age was 50 years, with one-fourth of patients older than 60 years. According to the revised Kiel classification for GI-NHL, 61% of patients presented with pure high-grade lymphoma, 9% high-grade NHL associated with residual low-grade lymphoma, and 30% had low-grade NHL. Nine percent presented with bulky disease, 5% with elevated LDH and 21% with a Karnofsky performance status (PS) < or = 80. RESULTS: Laparotomy with radical (108 patients) or palliative (15 patients) intent was performed in all patients who were not deemed at high risk of complication from major surgery. Complete removal of all measurable tumor was feasible in 101 patients, with no difference relative to primary site. Surgical morbidity and mortality were 11% and 2%, respectively. Overall, 83% of patients were treated with chemotherapy. Patients who did not receive systemic chemotherapy included 12 managed with surgery alone and 10 who received only postoperative irradiation mainly because of low-grade lymphoma with superficial disease. Of patients with limited disease, 99% achieved complete tumor remission. After a median follow-up of 73 months, 13 of 113 patients have relapsed, mostly (70%) outside the gastrointestinal tract. The actuarial 10-yr. freedom from progression (FFP) and overall survival (OS) were 84% and 86%, respectively. Aside from age, no other factor revealed a statistically significant impact on outcome. There was only a trend in favor of low-grade histology (FFP 97% vs. 79%), that failed to reach statistical significance. Of patients with advanced abdominal disease, 48% achieved complete remission with chemotherapy with or without prior surgical debulking. Actuarial 10-yr. FFP and OS were 44% and 42%, respectively. In this subset, tumor burden and LDH levels represented the most important prognostic factors affecting outcome. CONCLUSIONS: This retrospective study underscores the good results obtained in a wide and unselected population of patients with limited-stage primary GI-NHL following a combined-modality approach that included surgical debulking and systemic chemotherapy for most patients. Surgery alone can be considered adequate treatment for patients with low-grade NHL disease that does not infiltrate beyond the submucosa. Patients with advanced GI-NHL show a long-term outcome similar to that of patients with advanced NHL arising outside the gastrointestinal tract.

Aged↗
PubMed1993

High-dose sequential chemo-radiotherapy with peripheral blood progenitor cell support for relapsed or refractory Hodgkin's disease--a 6-year update.

BACKGROUND: Very few studies using high-dose therapy and autologous bone marrow transplantation have a long (i.e., > 3 years) follow-up. We report here the 6-year update of a study employing high-dose sequential chemo-radiotherapy in 25 patients with poor-risk Hodgkin's disease. PATIENTS AND METHODS: All patients were either refractory (7 patients) or partial responders (9 patients) or early relapses (9 patients) following induction chemotherapy consisting of MOPP/ABVD in 20 patients and MOPP/ABVD followed by salvage CEP for the remaining 5 patients. The high-dose chemo-radiotherapy regimen employed consisted in the rapid sequential administration of high-doses of cyclophosphamide, methotrexate, etoposide and total body irradiation plus melphalan. RESULTS: As compared to 4-year results, the 6-year probabilities of relapse-free survival, freedom from progression and overall survival were almost superimposable. In fact, during the two additional years elapsed since prior survey, only one event occurred (fatal cerebral hemorrhage) that was unrelated to Hodgkin's disease. In particular, the proportion of patients remaining event-free was 78% for those with short initial complete response and 31% for patients who had failed initial MOPP/ABVD. According to previous experience, both groups have a very low or no chance of long-term event-free survival when treated with standard-dose salvage chemotherapy. CONCLUSIONS: The very favorable long-term results of the high-dose sequential regimen together with its excellent tolerability and lack of early or late fatal toxicities, will assist clinicians in defining optimal timing for high-dose therapy in the management of Hodgkin's disease. According to a revised cost/benefit analysis, it would appear that, at present, the best timing of high-dose sequential therapy in patients failing MOPP/ABVD is at first early relapse.

Actuarial Analysis↗
PubMed1993

Second neoplasms following treatment of Hodgkin's disease.

In the past several decades, malignant lymphomas have been transformed from almost uniformly fatal illnesses to diseases that can be treated, with an expectation of long-term remission in a majority of patients. However, with the recognition of treatment efficacy also has come an appreciation of long-term sequelae. Among these late effects, the induction of a second cancer represents one of the most feared complications. For many years, acute nonlymphocytic leukemia has been the most frequently reported secondary malignancy; however, with increasing length of follow-up, solid tumors have replaced leukemia as the most commonly observed second cancers. The risk of second neoplasms depends on some treatment associations and on certain host-related factors. Less toxic treatment strategies need to be designed and appropriately tested in comparative trials. However, it is necessary to stress that, without effective therapy, the natural outcome of malignant lymphomas is death from progressive disease.

Acute Disease↗
PubMed1993

Combined modality treatment with primary CHOP chemotherapy followed by locoregional irradiation in stage I or II histologically aggressive non-Hodgkin's lymphomas.

PURPOSE: A single-center, prospective, nonrandomized trial was conducted to evaluate therapeutic results of a short-term program of chemotherapy followed by locoregional radiotherapy in stage I or II intermediate/aggressive non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: From 1985 to 1990, 183 consecutive patients with a diagnosis of NHL (Working Formulation [WF] E through J excluding Burkitt's type), Ann Arbor stage I or II, and no more than three sites of disease involvement were treated with four cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy (six cycles in partial responders). Radiation therapy to initial sites of disease involvement (40 to 44 Gy) and to proximal uninvolved nodal region (36 Gy) was delivered shortly after completion of the chemotherapy program. RESULTS: The complete remission (CR) rate was 98% at the end of combined therapy. Diagnostic excision of all measurable disease was performed in 33% of patients. In the remaining patients, 87% achieved CR with chemotherapy and 11% with radiation therapy, while three patients failed to achieve CR. After a median follow-up of 51 months, 26 patients have relapsed and 25 have died. The 5-year relapse-free and total survival rates were 83%. Aside from age older than 60 years, no other factor such as histology, stage, extranodal disease, bulky lymphoma, or abnormal lactic dehydrogenase (LDH) could predict for treatment outcome. There was a trend toward higher relapse rate for patients achieving CR at the time of radiation therapy (31%) as opposed to patients achieving CR with chemotherapy (15%) or with initial surgery (10%). Treatment was well tolerated and no deaths due to acute toxicity were observed. CONCLUSION: For patients who present with limited-stage, aggressive NHL, a short course of CHOP chemotherapy followed by locoregional irradiation is safe, highly effective, and curative for most. Therefore, at the present time this approach can be regarded as standard therapy for these patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Early stage Hodgkin's disease: ten-year results of a non-randomised study with radiotherapy alone or combined with MOPP.

From September 1976 to June 1982, 201 consecutive patients with stage I (A and B)-IIA Hodgkin's disease were stratified in two groups according to prognostic factors. The F group included 116 patients with favourable presentation: they were staged with laparotomy and treated with subtotal or total nodal radiotherapy alone. The U group included 85 cases with unfavourable presentation who were staged by laparoscopy and treated with 3MOPP (mechlorethamine, vincristine, procarbazine, prednisone)-radiotherapy-3MOPP. At 10 years the F group showed a freedom from progression (FFP) of 71% with significant difference between stage I and II (85% vs. 59%; P = 0.003) and an overall survival of 84%. The results of the U group were: FFP 83%, overall survival 74%, and the findings were not influenced by stage. FFP in patients with bulky vs. not bulky lymphoma was 70% vs. 87% (P = 0.04). No secondary acute non-lymphocytic leukaemia developed among patients treated with radiotherapy and in continuous complete remission, while acute leukaemia occurred in the F group patients who received salvage chemotherapy (4 of 31 cases) and in the U group (3 of 85 cases). Present results confirm the usefulness of radiotherapy alone in favourable pathological stage IA. All other disease stages will require a different strategy that should consist of radiotherapy combined with short-term effective regimens, such as ABVD (doxorubicin, bleomycin, vinblastine and decarbazine) or VBM (vinblastine, bleomycin and methotrexate) to reduce the incidence of MOPP-associated gonadal dysfunction and leukaemogenesis.

Adolescent↗
PubMed1992

Thyroid, pulmonary, and cardiac sequelae after treatment for Hodgkin's disease.

Modern therapy of Hodgkin's disease has produced the expectation of long-term survival for most patients. However, in the process of achieving the current success, a price has been paid in unwanted, delayed side effects. Apart from second malignancies and gonadal impairment, other adverse consequences can be identified. This paper will briefly summarize recent findings related to thyroid, pulmonary and cardiac dysfunction. Attention to treatment regimens and careful follow-up may help to prevent or manage these complications, which are uncommonly life-threatening. The desire to refine the treatment of Hodgkin's disease must not result in a reduction of the overall chance of cure.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Advances in the treatment of Hodgkin's disease.

Through the careful application of appropriate staging procedures and treatment modalities, at the beginning of the 1990s about 75% of patients with Hodgkin's disease can expect long-term remission or even cure. At present, radiotherapy remains the best therapeutic option for localized stages while advanced disease is cured by chemotherapy alone or chemotherapy combined with irradiation. In this decade, the challenge in the management of Hodgkin's disease will probably be represented by an optimal use of reasonably short-term chemotherapy regimens combined with limited-field irradiation in early stages and by an accurate evaluation of the best chemotherapy regimens for advanced disease. In the search for the optimal approaches to improve current therapeutic results, appropriate considerations should be given to the identification of effective treatment modalities with a minimum amount of acute and late toxicity.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

ABVD in the treatment of Hodgkin's disease.

This paper summarizes the clinical results achieved at the Milan Cancer Institute in advanced Hodgkin's disease through successive randomized studies performed during the last two decades. Long-term results confirm the therapeutic activity of a regimen containing bleomycin and doxorubicin, such as ABVD (doxorubicin/bleomycin/vinblastine/dacarbazine), as salvage treatment and as primary chemotherapy, either when combined with radiation or cyclically alternated with MOPP (mechlorethamine/vincristine/procarbazine/prednisone). Delayed iatrogenic morbidity (namely, sterility and leukemogenesis) was less frequently documented in ABVD-treated patients compared with MOPP-treated patients. Nevertheless, bleomycin- and anthracycline-containing regimens can be refined in the attempt to further decrease iatrogenic toxicity.

Adult↗