Erkki Heinonen

Adjuvant postoperative radiotherapy, chemotherapy, and immunotherapy in stage III breast cancer

One hundred twenty pathologically confirmed operable Stage III (T3N0–2) breast cancer patients were randomized to receive either postoperative radiotherapy or chemotherapy, or a combination of these, with or without levamisole immunotherapy. Radiotherapy was given to regional lymph node areas and chest wall. Chemotherapy consisted of 6 cycles of Adriamycin (doxorubicin) (45 mg/m2), vincristine (1.2 mg/m2) intravenously, and cyclophosphamide (200 mg/m2 for 5 days) perorally every 4 weeks. Peroral levamisole, 150 mg a day, 2 days weekly, was given as an immunotherapy. The 3‐year results are described in this article. The effect of levamisole on the prognosis cannot be evaluated yet because of the short follow‐up period. The disease‐free survival was almost equal in each patient group, however, some benefit was achieved by levamisole (a shift of disease‐free survival from 12 to 18 months). The patients receiving radiotherapy alone had the poorest prognosis: 68% had a recurrent tumor, and 57% were alive. In the chemotherapy group, the figures were 53% and 72%, respectively. Patients who received a combined treatment had the best prognosis: 13% had a recurrent tumor, and 90% survived 3 years. There was a statistically significant difference in the recurrence rate between any single therapy and the combined treatment (radiotherapy to combined treatment, P < 0.001, chemotherapy to combined treatment, P ± 0.01 chi‐square test). In overall survival, a statistically significant difference was reached between radiotherapy and combination treatment groups (P < 0.01, chi‐square test). Radiotherapy gave a good local control of the tumor, and chemotherapy decreased the number of metastases. The nonmetastatic axillary lymph node status and secondary amenorrhea or severe menstrual disturbances were of positive prognostic value. The side effects due to radiotherapy and chemotherapy were moderate and tolerable. The dose of Adriamycin had to be reduced only in four patients. All of the patients receiving chemotherapy had a transient total alopecia. Three of them had nonlethal arrhythmias, and one had skin rash. Levamisole was found very toxic with 9 cases of transient agranulocytosis, leading to the discontinuation of immunotherapy in 22 of 59 patients. Our results show that radiotherapy controls the tumor only locally and chemotherapy systematically, but the best patient‐saving results are achieved with a combination of radiotherapy and chemotherapy. The disease‐free and overall survival are statistically significant, and favor the combined therapy.

Adjuvant postoperative radiotherapy, chemotherapy, and immunotherapy in stage III breast cancer. II. 5-year results and influence of levamisole

One hundred twenty pathologically confirmed operable Stage III breast cancer patients were randomized to receive either postoperative radiotherapy or chemotherapy, or a combination of these, with or without levamisole immunotherapy. Radiotherapy was given to regional lymph nodes and chest wall. Chemotherapy consisted of six cycles of vincristine, doxorubicin, and cyclophosphamide. Radiotherapy provided local and chemotherapy systemic control over the tumor, but the best patient‐saving results were achieved with a combination of radiotherapy and chemotherapy. This clinical trial was commenced in 1976, and the first 60 of 120 patients also received oral levamisole, 150 mg/day, on 2 consecutive days weekly as immunotherapy. All patients were followed for at least 5 years. At this stage levamisole seems to increase disease‐free and overall survival in all three treatment arms (radiotherapy, chemotherapy, combined treatment). Significance is reached in disease‐free survival (P = 0.035) and overall survival, adjusted for all other treatment modalities (P = 0.019).

Levamisole in the treatment of stage II breast cancer: five-year follow-up of a randomized double-blind study

The effect of levamisole combined with postoperative radiotherapy in Stage II breast cancer was investigated in a double‐blind randomized study comprising 72 patients. All patients were followed for at least 5 years. Disease‐free survival was slightly prolonged in the levamisole group as a whole. Among postmenopausal patients, levamisole significantly increased both disease‐free and total survival (P = 0.003) and P = 0.008, respectively. The levamisole group also showed fewer distant metastases as the first sign of recurrence. Levamisole treatment was associated with a risk of granulocytopenia and agranulocytosis (10%), but, as in the authors previous studies, this seemed to be totally reversible and did not worsen the prognosis.

Oral carmofur in advanced gastrointestinal cancer.

One hundred and twenty-four patients with a diagnosis of metastatic gastrointestinal cancer and no prior therapy were included in this clinical study of carmofur monotherapy, 300–500 mg/m2 daily for 6 weeks. For the 115 evaluable patients, the response rates were 19.4% in gastric cancer, 27.2% in cancer of mobile colon, and 12.5% in rectal cancer. No objective responses were seen in 38 patients with pancreatic cancer, although the disease of 13 of these patients has remained stable over a considerably long period of follow-up. The toxicity profile was interesting; the main adverse effects were urinary bladder symptoms and flush. Hematologic toxicity was minimal. The treatment proved to be safe and could be used for outpatients.

Phase II evaluation of peroral carmofur, cyclophosphamide, and hexamethylmelamine as a second-line therapy in advanced epithelial ovarian carcinoma

A prospective phase II study was performed to evaluate the effect and tolerability of a peroral combination chemotherapy consisting of hexamethylmelamine, cyclophosphamide, and carmofur in patients with epithelial ovarian cancer previously heavily treated by cisplatin-based chemotherapy but no longer responding to it. Of the 27 patients 1 showed a clinical complete remission lasting 15+ months and 4 a partial remission of 6+ to 21 months. A further 7 patients had an unchanged situation of 4 to 13+ months. The median survival of the nonresponders was 3 months. The side effects were tolerable, mostly nausea and vomiting. Only 4 of 27 patients suffered from severe vomiting causing discontinuation of the therapy. The peroral ambulatory chemotherapy prolonged markedly the overall survival of about one-half of the patients with ovarian cancer who previously failed to respond to cisplatin-based chemotherapy.

Nandrolone decanoate added to tamoxifen in the treatment of advanced breast cancer

SummarySince 1980 we have been carrying out a prospective randomized trial comparing tamoxifen with the combination of tamoxifen plus nandrolone decanoate in advanced breast cancer. The tamoxifen dose is 30 mg daily and the nandrolone decanoate dose 100 mg i.m. once a week for four weeks and thereafter every other week. 98 post-menopausal patients have been evaluated for the response. The number of patients is 49 in both groups.The overall response rates (CR +PR) to tamoxifen and tamoxifen plus nandrolone decanoate were not significantly different; in the tamoxifen group the response rate was 49% and in the combination group 45%. The mean time to progression in tamoxifen group is over 13 months and in tamoxifen plus nandrolone decanoate group over 12 months. Our results do not suggest a synergistic effect from combining tamoxifen and nandrolone decanoate treatments. The response rates to tamoxifen at different sites of metastases were as follows: bones 47%, soft tissues 56%, and viscera 48%. The respective figures with the combination therapy were 36%, 64%, and 40%.Both treatments were well tolerated and in no patient was withdrawal of the therapy necessary. Mild virilization and hoarseness were experienced by all patients treated with nandrolone decanoate. Side-effects associated with tamoxifen were rare, although five patients experienced nausea and two had hot flushes.

Transfer factor immunotherapy in Hodgkin's and non-Hodgkin's lymphoma

SummaryHuman dialyzable transfer factor was administered in a double-blind fashion to patients with Hodgkins disease and non-Hodgkins lymphoma. Two groups were examined; patients with active disease and patients in remission. Parameters of cellular and humoral immunity were studied. The effect of transfer factor on the clinical condition was not evaluated.Transfer factor tended to intensify the skin test reactions of patients in remission to several recall antigens, but had no effect on the other parameters or the other patient group.