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Biomedical subjects

G Bonadonna

Publications and source records attributed to G Bonadonna.

At least 271 records · Page 15Linked to original sources

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↗

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↗

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↗

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↗

[Oral gestagen treatment of advanced breast neoplasms with norethisterone acetate].

The medical records of 84 postmenopausal women treated with oral norethisterone acetate (NTA) for advanced breast cancer have been analyzed retrospectively. Treatment was devoid of significant toxicity. 21 patients were not evaluable for treatment response, either due to insufficient data or inadequate tratment trial. Among the 63 evaluable patients, complete plus partial response was obtained in 21 (33.3%) with a median duration of 10 months. Disease stabilization was observed in 16 patients (25.4%) for a median duration of 5 months, while 26 patients (41.3%) showed progressive disease while on treatment. The best response was observed in women with predominantly soft tissue metastases (CR + PR: 34.9%) and aged over 70 (CR + PR: 48%). The literature on norethisterone acetate is reviewed and compared with the present results. The role of progestational agents in the treatment of advanced mammary carcinoma is discussed.

Administration, Oral↗

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↗

Adjuvant therapies of postsurgical minimal residual disease.

The review summarizes the most recent results obtained with present combined adjuvant strategy for the treatment of resectable cancer. Recent important randomized clinical trials, either unicentric or polycentric, are discussed. As far as pediatric tumors are concerned post-surgical adjuvant chemotherapy was proved to play a useful role in prolonging the disease-free survival in Wilms tumor, rhabdomyosarcoma, Ewing sarcoma. Results obtained in the treatment of medulloblastoma and osteogenic sarcoma need further investigations. In adult neoplasms the most important results with combined modality approach are presently being obtained in breast cancer and probably in melanoma. No consistent improvement by adjuvant chemotherapy has been observed in colorectal cancer.

Breast Neoplasms↗

Preliminary clinical experience with 4-epidoxorubicin in advanced human neoplasia.

4'-Epidoxorubicin (epi-DXR) was tested in 56 patients with various types of advanced malignancies. The pattern of acute toxicity was similar to that of doxorubicin (DXR), but epi-DXR produced a lower incidence of vomiting, stomatitis, alopecia, and myelosuppression. The study of cardiac toxicity, utilizing only noninvasive methods, indicated that epi-DXR also is cardiotoxic. The increase in the systolic time intervals after the first dose as well as after cumulative doses was slightly lower compared with that observed after DXR. Antitumor activity occurred in a variety of tumors including malignant melanoma, renal cancer, and rectal cancer, which are refractory to DXR. Present results suggest that further studies with epi-DXR are indicated.

Adolescent↗

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↗

Prolonged disease-free survival in MOPP-resistant Hodgkin's disease after treatment with adriamycin, bleomycin, vinblastine and dacarbazine (ABVD).

Twenty-one patients with advanced Hodgkin's disease resistant to MOPP (mechlorethamine, vincristine, procarbazine, prednisone) were treated with ABVD (adriamycin, bleomycin, vinblastine, dacarbazine). ABVD induced complete remission in 13 patients (62%) and partial remission in 2 (9.5%). In particular, complete response to ABVD was obtained in 7 of 13 patients who failed to respond to primary MOPP chemotherapy. After six cycles, no further therapy was given to patients in complete remission. At 36 months from starting ABVD, 69.7% of complete responders remain alive and free of disease, with a total survival of 73.4%. In contrast, none of the patients in whom partial response or nonresponse was observed was alive at 18 months. ABVD for six cycles was accompanied by mild and reversible toxicity. The results indicate that there is no cross-resistance between MOPP and ABVD. ABVD appears a simple effective, and tolerable multiple-drug chemotherapy for use in patients who are resistant to MOPP.

Adult↗