Small cell carcinoma of the lung: a combined modality treatment.
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Biomedical subjects
Publications and source records attributed to G Bonadonna.
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From September, 1972 to December, 1976, 102 consecutive patients operated on for glioblastoma multiforme were randomized, after total or subtotal tumor resection, to receive irradiation alone, irradiation plus BCNU or irradiation plus CCNU. BCNU and CCNU adjuvant chemotherapy was repeated every 6--8 weeks as long as the patients remained in complete remission. Patients were comparable for median age, type of surgery, and histological grade III and IV. Radiotherapy was administered at the tumor dose of about 5000 rads in all three groups. The percent of optimal dose administered was 96% for BCNU and 93% for CCNU. In the group treated with radiotherapy alone (32 cases) the median survival was 10.5 months, while in the groups treated with BCNU (34 cases) and CCNU (36 cases) the median survival was 12 and 16 months, respectively. Both relapse-free (P = 0.05) and total survival (P = 0.03) were significantly improved only in patients who were treated with radiotherapy plus CCNU compared to patients receiving radiotherapy alone after surgery. Present results show that in resectable glioblastoma multiforme, a slightly improved survival rate can be achieved by the prolonged use of adjuvant CCNU following maximal surgical resection and radiotherapy. The cure rate was not improved.
In hope of reducing the duration of adjuvant treatment in premenopausal patients with operable breast cancer and histologically positive axillary lymph nodes, a prospective controlled study was started in September 1975. A total of 160 patients were randomized to receive 12 cycles of adjuvant CMF, while 165 were allocated to receive 6 cycles. At 3 years from radical mastectomy, the relapse-free survival was 85.4% in the 12-cycle group compared to 82.6% for the 6-cycle subset (P = 0.29). In both treatment groups, the incidence of treatment failure was directly proportional to the number of involved axillary nodes and to the clinical tumor size. Drug-induced amenorrhea as well as estrogen receptor status failed to significantly affect the results obtained. Treatment failures were more often documented in distant sites, while only 4--5% relapse was observed in local-regional areas. Overall survival was also similar for both treatment arms (86.2% vs. 85.1%, P = 0.49). Toxicity was moderate and reversible and no drug-induced neoplasms were so far observed. Present results achieved with 6 cycles of adjuvant CMF appear encouraging. However, they are still too preliminary to recommend the routine use of 6 cycles instead of the classical 12 cycles.
Valuable information was collected on the medical history and clinical course of 1273 patients entered in clinical trials with Adriamycin (ADR) carried out in 12 European cancer centers. A coded patient form was used for the data collection carried out in each center by a qualified physician following a guideline which was discussed and accepted by all of the participants. The aim of the study was to define the incidence, characteristics, and possible co-factors of the cardiomyopathy (CMP) in patients treated with combination chemotherapy regimens including ADR. The mean total dose of ADR was 268 mg/m2 (range, 15--1251 mg/m2), and 5.1% of the patients received a total dose of greater than 550 mg/m2. A "definite" ADR-related CMP was observed in 1.7% of the cases; another 3% of the cases were reported as "possible" ADR-CMP since the role played by the drug could not be clearly defined. "Definite" ADR-CMP was fatal in eight patients (0.6%) while "possible" ADR-CMP was fatal in 13 patients (1.0%). Among the possible co-factors examined, the following ones were found to be significantly associated with the occurrence of a "definite" ADR-CMP: (a) total dose of ADR; (b) vincristine when given both before and concomitantly with ADR; (c) bleomycin when given before ADR; and (d) radiotherapy to the mediastinum when given concomitantly with ADR. Furthermore, none of 182 patients receiving ADR by slow infusion developed a "definite" ADR-CMP, while 2% of the patients treated by bolus injection did so. The occurrence of a "possible" ADR-CMP was found to be significantly associated with two pre-existing pathologic conditions (electrocardiogram [ECG] abnormalities and hypertension) but not with the treatment-related co-factors for the "definite" ADR-CMP mentioned above. Other variables examined, such as sex, age, cancer type, baseline liver function, and cyclophosphamide treatment, did not seem to influence the risk of ADR-CMP. Data on ECG changes occurring during ADR treatment were also reported and their incidence was found to be strictly related to the frequency of the ECG monitoring.
A phase I study of 4'-epi-Adriamycin (4'-epi-ADM) was performed in 22 patients with various types of advanced solid tumors. Very preliminary results would indicate that the drug produces a pattern of acute toxicity which is similar to that of Adriamycin. However, the incidence of vomiting, alopecia, and marrow suppression was less pronounced than that of Adriamycin. 4'-Epi-ADM prolonged the systolic time interval, although no patient presented clinical signs of cardiotoxicity. Two patients with renal carcinoma and malignant melanoma showed objective improvement. Present results suggest that further clinical studies with 4'-epi-ADM are indicated.
Two cases of Hodgkin disease, lymphocyte depletion type, with bronchial involvement are described. One patient revealed involvement of the right upper lobar bronchus, the other patient of the left main bronchus. The correct diagnosis was made by fiberbronchoscope examination with cytologic brushing and biopsy. That bronchial involvement by Hodgkin disease is very rare is confirmed by the literature, where only 20 cases have been so far reported.
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The clinical records and histologic material of 18 consecutive patients with malignant histiocytosis were reviewed. The age of the patients ranged from 20 months to 72 years (median 35 years). There were 14 males and 4 females (3.5:1). Lymph node and liver enlargement, fever, and skin nodules were the most common physical findings; and leukocytosis was frequently the most abnormal laboratory test. Seven of 18 patients died, and their survival ranged from 1 to 15 months (median 8 months) after histopathologic diagnosis. The histologic findings on lymph nodes, spleen, liver, bone marrow, and skin were investigated with special reference to both the cellular composition and the pattern of lymph node involvement. Vascular invasion of small perinodal vessels was observed in 4 fatal cases. The absence of capsular invasion and the lack of cohesiveness among atypical proliferating histiocytes of malignant histiocytosis appeared to be inconstant. Sequential lymph node biopsies revealed in later stages the extension of the histiocytic proliferation from the sinuses into the cords and the complete obliteration of the nodal structures. The radiologic investigations yielded numerous pathologic findings that were consistent with the dissemination of the disease. Complete response to initial treatment was achieved in patients that were treated with radiotherapy and/or chemotherapy. Complete response with chemotherapy was achieved only when the treatment included adriamycin. The histologic and clinical features of the present series provide future evidence for the recognition of malignant histiocytosis as a distinct clinical and pathologic entity.
The records of 716 consecutive patients with breast cancer randomized from January 1964 to January 1968 between radical and extended radical mastectomy not followed by postoperative radiation therapy were reviewed. Relapse and survival rates were related to different patterns with the intent to define, on clinical basis, the high-risk groups in whom systemic adjuvant treatment can be attempted. The 10-year relapse rate was 52.9% for the whole series. In patients with negative axillary nodes (N-) this finding was 27.9% compared to 75.5% for patients with positive nodes (N+ 1-3: 66.5%, N+ greater than 3: 83.6%). The relapse rate was also affected by concomitant involvement of internal mammary nodes (IMN): N- IMN+: 60%, N+ IMN+: 96.7%. The corresponding 10-year survival rates were as follows: 59.7% (total), 81.9% (N-), 39.6% (N+), 53.7% (1-3), 25.6% (greater than 3), 45.8% (N- IMN+), 20.5% (N+ IMN+). In N+ patients relapse and survival rates were directly proportional to the size of primary tumor, while this trend was not present in N- patients. Location of primary tumor as well as menopausal status showed no direct effect on relapse and survival. In both nodal groups the sites of first relapse were documented to occur preferentially in distant organs and tissues.
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The results of a prospective controlled study with alternating cycles of two effective non-cross resistant combinations in advanced breast cancer are reported. The two combinations consisted of adriamycin plus vincristine (AV) and cyclophosphamide, methotrexate and fluorouracil (CMF). The study was carried out with the main intent to obtain a higher incidence and a longer duration of response compared to that obtained with either combination alone. A total of 110 evaluable patients (55 for each treatment group) not previously treated with chemotherapy were randomly allocated to receive either Therapy A (2 AV followed by 2 CMF) or Therapy B (2 CMF followed by 2 AV). Complete plus partial response (53% vs 60%) as well as duration of remission (11 vs 12 months) were similar in both treatment groups. At the time of present analysis, 20 patients died from cancer (Therapy A: 9; Therapy B: 11) and in 9 of them death occurred during the first 12 months. The administration of sequential combinations was no more toxic than the administration of either combination alone.
Combined treatment modality was applied in 110 consecutive women with primary inoperable (T3b-T4) Breast cancer. Treatment was started with four cycles of adriamycin plus vincristine (AV). This was followed in responders by high-energy radiotherapy (RT). At the end of combined therapy, patients in complete remission (CR) were randomized to either no further treatment or six more cycles of chemotherapy. AV induced objective response in 89% of patients (complete 15.5%, partial 54.5%, improvement 19%). At the end of RT, 81% of 98 (82.7%) patients responding to AV were classified in CR. The median duration of CR was 15 months. The median free interval was statistically prolonged by additional chemotherapy. The three-year survival was 52.8%. Altogether, present findings indicate that combined treatment modality has improved the three-year survival compared to the previous series treated with radiotherapy alone. However, to achieve a satisfactory control of T3b-T4 breast cancer a more aggressive and prolonged treatment is required.
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