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Biomedical subjects

P Valagussa

Publications and source records attributed to P Valagussa.

At least 163 records · Page 9Linked to original sources
PubMed1982

Clinical trials on adjuvant therapies in cancer: short-term and long-term results.

Short-term results of adjuvant treatments of cancer have been reported all over the world with the specific aid of reducing the period required to determine the cure rate of a potentially curative treatment. While this motivation is important, short-term analyses are not totally unbiased and they require careful evaluation. The most peculiar aspect is that short-term results should properly predict long-term results. Therefore, a complete knowledge of the natural history of the disease under evaluation, an adequate number of patients, adequate follow-up of these patients, as well as a proper statistical analysis are essential to derive useful information from intermediate analysis. This paper attempts to point out these aspects and summarizes the experience of the Istituto Nazionale Tumori of Milan in two different adjuvant studies (breast cancer and non-Hodgkin's lymphomas).

Antineoplastic Agents↗
PubMed1982

Absence of treatment-induced second neoplasms after ABVD in Hodgkin's disease.

One of the most serious complications of successful treatments for Hodgkin's disease is an increased incidence of acute nonlymphocytic leukemia (ANLL) and other malignancies. A retrospective analysis carried out on 1032 consecutive patients with Hodgkin's disease admitted to our Institute between 1965 and 1978 and treated with radiotherapy (RT) or chemotherapy or both modalities revealed that within 10 yr from initial therapy. ANLL was documented in 3% of patients, and over a comparable period of time 7.9% of patients developed other malignancies. ANLL was observed only in patients treated with chemotherapeutic regimens containing alkylating agents and/or procarbazine either alone (2.3%) or associated with RT (4%). Other second tumors were documented in patients given RT with or without chemotherapy. No second malignancies were observed in patients given ABVD (adriamycin, bleomycin, vinblastine, and dacarbazine) with or without RT. The incidence of ANLL was higher in patients given chemotherapy as salvage treatment upon relapse following primary irradiation (6.1%) compared to patients initially treated with combined modality (1.5%). The difference, however, failed to reach statistical significance. Since our analysis supports the evidence of a major role played by alkylating agents, procarbazine, and RT in inducing second malignancies, regimens not containing there drugs or their administration through treatments of different intensity warrant careful consideration.

Actuarial Analysis↗
PubMed1982

Cyclic delivery of MOPP and ABVD combinations in Stage IV Hodgkin's disease: rationale, background studies, and recent results.

This paper summarizes the experience achieved at the Cancer Institute of Milan with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy in various stages of Hodgkin's disease, with special emphasis on the cyclic delivery of mechlorethamine, vincristine, prednisone, and procarbazine (MOPP) and ABVD in the primary treatment of stage IV disease. Six cycles of ABVD yielded a complete remission (CR) rate (71%) similar to that of MOPP (63%). ABVD combined with radiotherapy in 153 patients with stage IIB, IIIA, or IIIB disease was superior to MOPP plus radiotherapy in the CR induction (94% vs 79%, P less than 0.01), particularly in the presence of nodular sclerosis histology (P less than 0.03) and B symptoms (P = 0.01), as well as in the relapse-free survival of patients with pathologic stage IIIA disease (ABVD, 100%; MOPP, 68%; P = 0.02). Total survival was similar between the two treatment groups, but, compared to MOPP, ABVD chemotherapy was associated with a lower incidence of delayed toxic effects such as azoospermia, prolonged amenorrhea, and cancerigenesis. ABVD induced CR in 59% of 54 patients resistant to MOPP; 37.5% of the complete responders remain alive and disease-free at 5 years. The cyclic delivery of MOPP and ABVD was significantly superior to that of MOPP alone in terms of CR (92% vs 71%; P = 0.02), freedom from disease progression (70% vs 37%; P less than 0.0001), and relapse-free survival (77% vs 47%; P less than 0.01) at 5 years. Toxic effects were similar between the two treatment groups, but there was a higher incidence of vomiting and alopecia following ABVD chemotherapy; in the group given MOPP alone, one patient who had previously failed extensive irradiation developed acute nonlymphocytic leukemia. ABVD is confirmed to be an effective regimen that is non-cross-resistant to MOPP and devoid of late morbidity. Therefore, its administration, when alternated monthly with MOPP, offers the possibility to improve the cure rate of Hodgkin's disease.

Adult↗
PubMed1981

Multimodal treatment in operable breast cancer: five-year results of the CMF programme.

The five-year results of a prospective randomised trial of radical mastectomy (179 patients) versus radical mastectomy followed by adjuvant chemotherapy (207 patients) were analysed. Chemotherapy consisted of 12 monthly cycles of cyclophosphamide, methotrexate, and fluorouracil (CMF). Both relapse-free survival (controls 44.6%, CMF group 59.5%) and total survival (controls 66.2%, CMF group 78.4%) were significantly improved. The findings were related to the number of diseased axillary nodes and amount of drug administered, and were independent of CMF-induced amenorrhoea. Menopausal state alone appeared to affect the five-year results only when the amount of drug administered was not taken into account. Salvage treatment at first relapse failed to improve total survival in the controls compared with the CMF group. Acute toxic manifestations were moderate and reversible. Chronic organ damage and increased incidence of second neoplasms (controls 1.7%, CMF group 1.4%) were not observed. The multimodality approach to treatment of primary breast cancer is a new and important advance. This and other studies are continuing.

Adult↗
PubMed1981

Usefulness of chest and skeletal survey to assess the time of relapse in breast cancer.

The pertinent radiographs of 151 patients treated with radical mastectomy who showed relapse in the chest and/or in the skeleton as first site were reevaluated. Diagnostic accuracy was calculated by comparing the first examination considered as positive with the previous ones reported as negative. For chest lesions the accuracy was 80% (70% for parenchymal nodular densities), with no difference between symptomatic and asymptomatic patients. For bone metastases retrospective evaluation confirmed the radiological report (i.e., the time of relapse), in 73.8%, with a value of 89.7% in symptomatic and 53.4% in asymptomatic patients. The site of involvement and morphological characteristics of the lesions did not influence the diagnostic accuracy. Therefore chest examination and, for symptomatic patients, radiographic bone survey still represent a useful modality to assess the diffusion of breast cancer. For asymptomatic patients other modalities, such as bone scan and biochemical tests, should be utilized.

Bone Neoplasms↗
PubMed1981

Inefficacy of internal mammary nodes dissection in breast cancer surgery.

From January 1964 to January 1968, 737 patients with breast cancer were randomized at the Cancer Institute in Milan to undergo either Halsted mastectomy or Halsted mastectomy with internal mammary node dissection; 716 were considered evaluable. The series was part of an international cooperative study. The two groups of patients were comparable in age, menopausal status, quadrant distribution, and frequency of axillary metastases. No patients received postoperative radiotherapy or adjuvant treatments. At ten years, no difference was found in either in the length of disease-free or overall survival in the two series. The overall survival was 60.7% in patients treated with Halsted mastectomy and 57.0% in patients treated with Halsted mastectomy plus internal mammary dissection. In no subgroups was a statistically significant difference found. In the series treated by extended mastectomy, the incidence of internal mammary metastases was 20.5% (24.6% in cases with tumor in medial or central quadrants and 17.7% in cases with tumor in lateral quadrants). The follow-up of the patients treated by Halsted mastectomy showed that only 15 had a parasternal recurrence; the expected number was 75. In nine patients, parasternal recurrences were the first site of relapse of the disease. All of them were treated with radiotherapy, and in four a complete control was obtained.

Adult↗
PubMed1981

Dose-response effect of adjuvant chemotherapy in breast cancer.

We retrospectively analyzed the role of the dose level of CMF (cyclophosphamide, methotrexate, and fluorouracil) in postoperative adjuvant chemotherapy for breast cancer and in chemotherapy for metastatic breast cancer. There was a clear dose-response effect, indicating that CMF was useful only when given in a full or nearly full dose (greater than or equal to 85 per cent of the planned dose). Those given adjuvant therapy with 12 cycles of CMF at this dose level had a five-year relapse-free survival of 77 per cent, as compared with 45 per cent of patients treated only with radical mastectomy (P = 0.0001). In contrast, a subgroup receiving less than 65 per cent of the planned dose had a five-year survival without relapses of 48 per cent and a five-year survival with relapses of 67 per cent. These results are similar to those observed in a control group. With each dose level, the results at five years were influenced by the number of axillary lymph nodes involved but not by menopausal status. Our findings indicate that it is necessary to administer combination chemotherapy at a full dose to achieve clinical benefit.

Aged↗
PubMed1981

Prospective study with HEXA-CAF combination in ovarian carcinoma.

The value of combination chemotherapy with HEXA-CAF was analyzed in 31 patients with histologically documented epithelial ovarian cancer in advanced stages (minimal or gross disease). No patient had been previously treated with chemotherapy. Peritoneoscopy with diaphragmatic inspection, peritoneal cytology, lymphography, and chest X-ray were routinely used in staging and restaging the patients. Complete (CR) plus partial (PR) responses were obtained in 13/31 fully restaged patients (41.9%). CR was recorded in seven patients (22.5%) and PR in six patients (19.3%). Remission duration was significantly longer in patients who achieved CR (20 months) than in those who attained PR (9.5 months) (P Less Than 0.01). In all treated patients the median duration of survival was 16.5 months. Survival was significantly longer in patients with CR than in patients who did not achieve CR (P Less Than 0.05). Nevertheless, considering the rate of CR in patients with gross disease (20.6%), HEXA-CAF combination seems a useful but not yet a hopeful treatment for patients with advanced ovarian carcinoma.

Altretamine↗
PubMed1981

Adjuvant CMF effect on site of first recurrence, and appropriate follow-up intervals, in operable breast cancer with positive axillary nodes.

From June 1973 to May 1978 a total of 845 patients with operable breast cancer were entered into different adjuvant programs. The medical records of the 278 patients showing relapse were carefully re-evaluated to assess the pattern(s) of first recurrence and the consistency of follow-up modulation. Ninety-one of 179 patients treated with surgery alone, 130 of 414 given 12 cycles of adjuvant CMF and 57 of 252 treated with 6 cycles of CMF showed treatment failure within 5 years from radical mastectomy. The frequency of new disease manifestations was significantly affected by primary treatment, since patients given adjuvant CMF showed a lower tendency to recur in local-regional area(s) and in bone(s). However, in relapsed patients, patterns of new lesions were not substantially altered by type of primary treatment. The most frequently involved sites were soft tissues (37.8%) and bones (37%) followed by viscera (34.2%). Retrospective evaluation of X-rays revealed that in 26.2% of osseous metastases, diagnosis could have been assessed earlier, with a median delay of 4 months (range 1-8). Present analysis also revealed that short-term repeated X-ray examinations yielded findings more controversial than reliable for assessing the exact time of relapse, thus preventing firm conclusions in the presence of suspicious recurrence. A new follow-up schedule after completion of adjuvant chemotherapy is proposed, since on the basis of our experience, in asymptomatic patients frequently repeated examinations are not necessary and some can safely be omitted.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1981

Labeling index as a prognostic marker in non-Hodgkin's lymphomas.

The labeling index (LI) was determined at the time of initial diagnosis of 88 untreated adults with non-Hodgkin's lymphomas. The frequency distribution of low (less than or equal to 4%) and high (> 4%) LI between tumors with nodular and diffuse histologic patterns was significantly different (P < 0.001): The median LI was about four times greater for diffuse lymphomas than for nodular lymphomas. LI was not correlated with either disease extent or systemic symptoms. In patients with tumors of low LI, complete remission occurred in 86% of those with modular lymphomas and in 74% of those with diffuse lymphomas. These values were significantly different from the 17 and 39% observed respectively for nodular and diffuse lymphomas with high LI. Patients with low LI had greater actuarial 4-year survival than did those with high LI (P < 10(-7)). Highly significant differences between the two kinetic groups were also observed within nodular and diffuse patterns. However, whereas the difference for nodular lymphomas was independent of histologic subtype and stage, this was not always true for all subtypes of diffuse lymphomas. LI could be a useful marker to identify prior to treatment the patients who could enter complete remission and have favorable survival. Its clinical relevance as a prognostic factor appeared superior to the Rappaport histologic classification and pathologic stage, especially in patients with nodular histology.

Actuarial Analysis↗
PubMed1981

Multimodal treatment for locally advanced breast cancer. Result of chemotherapy-radiotherapy versus chemotherapy-surgery.

In a prospective randomized study, the efficacy of two combined modality approaches (chemotherapy plus radiotherapy or chemotherapy plus mastectomy) was tested in a total of 132 women with locally advanced breast cancer. Chemotherapy consisted of Adriamycin plus vincristine (AV) administered for three cycles before either local-regional modality and subsequently for seven additional cycles. Although a higher proportion of women achieved complete remission after mastectomy (100%) compared to women given radiotherapy (60%), the total response rate at the end of combined modality was identical (75%). There was no significant difference between the two treatment groups in terms of patterns of treatment failure, median duration of response, and total survival. Treatment was not influenced by menopausal or estrogen receptor status. Two patients of the surgical group showed Adriamycin-induced cardiomyopathy after cumulative doses less than 500 mg/m2. The results of present study failed to indicate that surgery per se improved the overall results including local control, over radiotherapy in a combined modality setting.

Adult↗
PubMed1981

Adjuvant combination chemotherapy for operable breast cancer. Trials in progress at the Istituto Nazionale Tumori of Milan.

Adjuvant trials ongoing at the Istituto Nazionale Tumori of Milan for operable breast cancer with nodal involvement are reviewed in this paper. In the first trial (cyclophosphamide, methotrexate, 5-fluorouracil [CMF] versus control), the early 5-year results confirm the usefulness of combination chemotherapy in significantly affecting the relapse-free survival (RFS) and total survival rates. The degree of axillary node involvement remains the most important prognostic indicator also in patients receiving adjuvant chemotherapy. The contention concerning the therapeutic effect of CMF in pre- versus postmenopausal women is overcome by the observation that about 80% of patients receiving greater than 85% of the planned dose are surviving relapse free at 5 years regardless of their menopausal status. The 3-year results of the second CMF trial indicate that both RFS and total survival are comparable between the groups receiving 12 or 6 cycles of adjuvant CMF. The results were not affected by drug-induced amenorrhea nor by estrogen receptor status. Provided the percent of dose administered is high, there is probably no real advantage in prolonging CMF chemotherapy beyond the sixth month. However, the results are still preliminary.

Aged↗
PubMed1980

Second malignancies in Hodgkin's disease: a complication of certain forms of treatment.

A total of 764 patients with Hodgkin's disease treated with radiotherapy (RT) or chemotherapy or both were reviewed 3-186 months (median 43 months) after initial treatment to assess the incidence of second malignancies. Incidence of solid tumours and acute non-lymphoblastic leukaemia (ANLL) were calculated by a life-table method and percentages of patients affected derived from life-table plots. Within 10 years after initial treatment the overall incidence of second solid tumours was 7.3%, and over a comparable period 2.4% of patients developed ANLL. Solid tumours occurred only in patients given RT with or without adjuvant chemotherapy, and ANLL occurred only after treatment with MOPP (mustine, vincristine, procarbazine, and prednisolone) or modified MOPP regimens. Neither solid tumours nor ANLL occurred in patients given ABVD (adriamycin, bleomycin, vinblastine, and dacarbazine). The highest incidence of leukaemia (5.4%) occurred after treatment with extensive RT plus (5.4%) occurred after treatment with extensive RT plus MOPP; hence the benefits of this approach in Hodgkin's disease must be weighed against its carcinogenic potential.

Adult↗
PubMed1980

Estrogen-receptor status and response to chemotherapy in early and advanced breast cancer.

The value of estrogen receptor (ER) status in the prediction of tumor response to combination chemotherapy was retrospectively analyzed in breast cancer patients selected for prospective controlled trials of chemotherapy (85 with advanced disease and 256 with operable tumors). All patients were previously untreated with either chemotherapy or endocrine therapy, and in all instances drug therapy was applied at the time of primary treatment. The ER status was considered positive in 54% of women with advanced disease and in 70% of women with operable breast tumor and positive axillary nodes, respectively. About 12% of patients were considered to have borderline ER. The response to drug therapy (complete plus partial remission in advanced breast cancer and 3-year relapse-free survival after mastectomy, respectively) was not significantly different between ER+ and ER- tumors. The comparative results of ER+ vs ER- patients were similar whether the cutoff point for ER+ t-mors was greater than 5 or greater than 10 fmol/mg cytosol protein. The present results indicate that in advanced and early breast cancer combination chemotherapy is effective regardless of ER status. Therefore, in the presence of ER+ tumors there is no reason to delay the early administration of effective chemotherapy. This is particularly true both in the presence of rapidly progressing metastatic disease and in the adjuvant setting.

Breast Neoplasms↗
PubMed1979

Clinical classification and survival in chronic lymphocyte leukemia.

Sixty-one consecutive patients with chronic lymphocytic leukemia (CLL) treated at the Istituto Nazionale Tumori of Milan from September 1962 to August 1976 were classified according to the staging system of Rai et al. (16). Analysis of this series showed the following median survival (in months) from diagnosis: stage 0-I, 73; stage II, 44; stage III-IV, 32. In 11 patients without peripheral palpable adenopathies, the lymphangiogram showed abnormal retroperitoneal lymph nodes. Therefore, the initial stage was changed from 0 to I in 5 cases. The median survival for the entire series was 50 months. Patients with "indolent" disease had a median survival of 52 months, while in patients with "active" CLL, the median survival was 32 months. Both sex and age were shown to be poor predictors of survival. Increased duration of survival was observed in patients with less compared to those with more than 30,000 lymphocytes/mm3 (66 versus 41 months). The method of staging proposed by Rai et al. and utilized to classify this series at the time of diagnosis was confirmed to be a reliable predictor for survival.

Adult↗