Adjuvant clodronate therapy in patients with locally advanced breast cancer--long term results of a double blind randomized trial. Slovak Clodronate Collaborative Group.

Between March 1990 and May 1993 seventy three patients with previously untreated breast cancer, Stage III or IV without osseal metastases were randomized to sodium clodronate 1600 mg daily p.o.(arm A = 37 patients) or placebo (arm B = 36 patients) over 2 years, additionally to standard therapy. Ten patients were not evaluable for response because of short duration of therapy (less than 2 months). Bone metastases developed in 30% of patients in arm A and 23% patients in arm B. Median time to appearance of bone metastases was 13 months in arm A and 28 months in arm B. Non-bone metastases appeared in 48% patients in arm A and in 48% patients in arm B. Time to development of non-bone metastases was 20 months in arm A and 16 months in arm B. Five-year survival was 41% in arm A and 39% in arm B. There were no significant differences between the treated and control arms.

Intensive combination chemotherapy (TTL-I protocol) of large cell and immunoblastic lymphomas--long-term observation.

Fifty patients with advanced (Stage III and IV) large cell and immunoblastic lymphoma were treated with eight 4-week courses of chemotherapy. The first two identical A courses were composed of high dose cyclophosphamide, vincristine, 5-day administration of bleomycin, 2-week prednisone, and methotrexate with calcium leucovorin. The next two "B" courses were composed of vincristine, 3-day administration of doxorubicin together with bleomycin, and prednisone. The next two "C" courses were composed of cyclophosphamide, vincristine, bleomycin, prednisone, methotrexate, and calcium leucovorin. The last two "D" courses were the same as "B" courses. CNS prophylaxis was done with intrathecal methotrexate. Fourty-two patients (84%) achieved complete remission, 7 patients entered partial remission, and 1 patient failed to respond. The median survival of all groups was 80 + months (range 2-181 + months). Nine patients relapsed (21%), and seven patients died in complete remission, three of them died of toxicity. The most frequent toxicity was myelosuppression, mostly leukopenia, frequently followed by infection, sometimes severe. Neurotoxicity and stomatitis were frequent, but usually not severe. Two patients developed secondary malignancies. Most of the patients (54%) are alive without evidence of disease at present.

Comparison of two non-cross-resistant combinations (ABVP/LOPP) with COPP plus bleomycin in the treatment of advanced Hodgkin's disease.

Eighty patients with advanced Hodgkin's disease were randomized either to treatment with combination of doxorubicin, bleomycin, vinblastine, and prednisone (ABVP), alternating with lomustine, vincristine, procarbazine, and prednisone (LOPP)--Group A, or to combination of cyclophosphamide, vincristine, procarbazine, prednisone, and low dose of bleomycin (COPP-Bleo)--Group B. Thirty-nine out of 41 patients (95%) in Group A achieved complete remission (CR) as compared to 25 CR in 39 patients (64%) in Group B. Patients with systemic symptoms, bulky disease, and nodular sclerosis achieved significantly more CR after treatment with ABVP/LOPP regimen than with COPP-Bleo regimen. Ninety percent of patients are alive in Group A (median observation time 97+ months) as compared to 58% in Group B (median observation time 97+ months). Ninety-two percent of complete responders are in CR in Group A as compared to 53% of complete responders in Group B. These differences between both groups are significant. More serious (WHO grade III and IV) myelosuppression as well as stomatitis and alopecia were observed in Group A. Gastrointestinal toxicity and neurotoxicity was more frequent in Group A. No patient died due to toxicity in Group A as compared to one patient in Group B. Non-cross-resistant alternating regimen ABVP/LOPP was more effective in the treatment of advanced Hodgkin's disease than the COPP-Bleo regimen, especially for patients with advanced Stage IVB Hodgkin's disease.

The status of nuclear medicine techniques in the diagnosis of bone metastases in breast cancer.

In this article, the authors present their experience with the diagnosis of bone metastases in patients with breast cancer using bone scintigraphy with 99mTc phosphonate and radioimmunological determination of carcinoembryonic antigen (CEA) and tissue polypeptic antigen (TPA). In a group of 395 patients, there was agreement between tumour markers (CEA, TPA) and the results of bone scintigraphy in 331 cases (84%)--negative in 193 cases (49%) and positive (i.e. in terms of bone scintigraphy results and the presence of at least one tumour marker) in 138 cases (35%). On the basis of this good agreement of the results between bone scintigraphy and CEA and TPA levels, the authors recommend the following algorithm in monitoring patients with breast cancer: follow-up of tumour markers at several-month intervals and, any increase in their levels will refer the patient to further examination using imaging techniques including bone scintigraphy.

Treatment of advanced Hodgkin's disease with modified MOPP regimens. A long-term observation.

Fifty-three patients with advanced Hodgkin's disease, most of them previously treated, received 8 to 16 courses of modified MOPP regimens (nitrogen mustard replaced by trichlormethine in arm A, with addition of vinblastine to the 4-drug regimen in arm B, and alternation of three drugs--trichlormethine, vincristine, and prednisone--with probably non-cross resistant two drugs--vinblastine and procarbazine in arm C). Thirty patients (57%) achieved complete remission. Higher complete remission rate and longer survival was recorded in patients treated with 5-drug regimens (arms B and C) as compared to the 4-drug regimen (arm A), but the differences were not significant. Higher complete remission rates were observed in asymptomatic patients, females, and patients with lymphocyte predominance and nodular sclerosis subtypes of Hodgkin's disease. Besides expected short-term toxicity, 4 out of 30 complete responders developed secondary malignancies (two acute myeloblastic leukemias, one hepatocellular carcinoma, and one cerebellar astrocytoma). Several other patients had serious toxicity which could be attributed to chemotherapy. Twenty-eight percent of the patients has been alive 15 to 18 years since the start of this study.

Significance of carcinoembryonic and tissue polypeptide antigen determination in the diagnosis of metastases in breast cancer.

A radioimmunological assay of CEA and TPA levels in breast cancer patients revealed a 93.7% concordance of negative and 93.4% of positive values with the clinical activity of the disease. In 26 out of a group of 38 patients (68.4%) with progressive breast carcinoma, an enhanced CEA and TPA level was the first indicator of the presence of metastases. In view of the results obtained, the authors consider this procedure to be a suitable method for monitoring and early detection of metastases in patients with breast cancer.

Treatment of adult acute lymphoblastic leukemia: results of two trials.

Thirty eight patients with acute lymphoblastic leukemia were treated protocol 0171 (VCR, PRED, MTX, cyclophosphamide +/- +/- 6-MP) and protocol 0276/A (VRC, PRED, L-ASP, MTX, 6-MP, cyclophosphamide). Overall complete remission rate in both studies was 84--85%, and additional treatment in protocol 0171 resulted in complete remission rate of 92%. Median duration of complete remission in protocol 0171 was 23 months and median survival of all patients was 33 months. Six patients randomized to regimen "A" (without 6-MP in intensification) had median duration of complete remission 8 months and media survival was 13 months. Seventeen patients treated with regimen "B" (with 6-MP in intensification) had median duration of complete remission 25 months and median survival was 39 months. Median survival of patients allocated on protocol 0276/A in 21+ months and median duration of complete remission is 23 months at present. Twelve percent of patients treated with the best regimen have survived more than 66 months in continuous complete remission. The incidence of drug related death in complete responders was 6%. The relapses were most frequent during the first two years of remission. Extramedullary leukemia as the initial site of relapse was observed in 9% of patients.

Significance of radioimmunoassay of human chorionic gonadotropin and alpha fetoprotein in nonseminomatous germ cell tumors of the testis.

Radioimmunoassays of human chorionic gonadotropin (HCG) and alpha fetoprotein (AFP) made in 49 patients with nonseminomatous testicular tumors have shown that these investigations make the diagnosis more precise, permit to follow up the dynamics of the course of the disease and the effectiveness of treatment and may help to reveal the presence of otherwise undetectable tumorous metastases. The significance of the these assays is enhanced if the two tumorous proteins are investigated in parallel. The results proved rightly positive in 43 (87.8%) and falsely negative in 6 (12.2%) of the patients. The absence of HCG and AFP production in some of the patients with an active disorder has not as yet been elucidated.

The response rate at chemotherapy in advanced Hodgkin's disease reflected by peripheral lymphocyte count.

Forty patients with advanced Hodgkin's disease stage III and IV were treated with combination chemotherapy. Absolute lymphocyte count in the peripheral blood was determined before start to chemotherapy. Higher levels of lymphocytes in the peripheral blood were associated with higher chemotherapy response rates. This difference was statistically significant (P less than 0.05).