mitolactol and Neoplasm-Metastasis

Patients who have metastatic breast cancer are seldom curable. Chemotherapy given by conventional doses and schedules generally produces complete remissions in 10% to 20% of patients. This study sought to determine 1) whether a combination of dibromodulcitol, Adriamycin, vincristine, tamoxifen, Halotestin, and methotrexate with leucovorin rescue (DAVTHML) can produce a complete remission rate of 50%; and 2) the toxicity of this combination in patients with chemotherapy-naive metastatic breast cancer. Patients were treated with six 28-day cycles of DAVTHML induction chemotherapy consisting of dibromodulcitol, 135 mg/m2 perorally days 1 to 10; Adriamycin 45 mg/m2 intravenously day 1; vincristine, 2 mg intravenously day 1; tamoxifen and Halotestin, 20 mg perorally daily; methotrexate, 800 mg/m2 intravenously days 15 and 22; and leucovorin, 15 mg/m2 perorally every 6 hours for 9 doses, starting 4 hours after methotrexate. After induction, patients who had stable disease or a partial response were treated with a cyclophosphamide, methotrexate, and 5-fluorouracil-based regimen (CMF). Patients in complete remission were treated with three additional cycles of DAVTHML after achieving complete remission and then observed off therapy until relapse, when DAVTHML was to be given again. Fifty-eight patients were included in this study. During induction, 26% of eligible patients experienced a complete remission; overall response rate was 80%. The median time to treatment failure and the median survival time of eligible patients was 11.1 and 24.0 months, respectively. This did not change significantly when all the patients were included in the evaluation. The 3-year and 5-year survival rates were 37% and 11%, respectively. Ninety percent of the eligible patients experienced grade III or IV toxicity. They were leukopenia (75%), anemia (20%), thrombocytopenia (20%), and vomiting (17%). No lethal toxicity was documented during therapy; however, 1 patient later died of myelodysplastic syndrome induced by dibromodulcitol. The overall response and complete remission rates from our study were encouraging. The toxicity of DAVTHML was tolerable, with the exception of myelodysplastic syndrome from dibromodulcitol. The concept of using mid-cycle nonmyelosuppressant agents to increase complete remission rate is feasible.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Doxorubicin; Female; Fluoxymesterone; Humans; Methotrexate; Middle Aged; Mitolactol; Neoplasm Metastasis; Pilot Projects; Remission Induction; Survival Analysis; Tamoxifen; Vincristine

To investigate the therapeutic value of reinduction with the same cytostatic treatment that had been used in induction treatment for women with metastatic breast cancer.. One hundred six women with metastatic breast cancer were given dibromodulcitol (mitolactol), doxorubicin, vincristine, tamoxifen, and fluoxymesterone (DAVTH) for 6 months of induction treatment, then randomized to receive one of two chemotherapy regimens if they had obtained an induction partial response (PR) or no change (NC), or to receive observation versus chemotherapy if they had obtained an induction complete response (CR). Patients were then retreated with DAVTH reinduction after relapse.. Seventy-four patients were eligible or had minor reasons for ineligibility. Severe or life-threatening toxicity was documented in 46%, and lethal toxicity in 4%. Eighteen percent had a response on reinduction (zero of 16 induction nonresponders, 15% induction PR, 44% induction CR). The median time to treatment failure (TTF) from reinduction was 3 months, and the median survival duration from reinduction was 14 months. In a logistic model, factors associated with more reinduction responses were observation after induction CR (P = .002) and age greater than 55 years (P = .04). Time since induction was not significant.. Reinduction of response after treatment failure remains a therapeutic problem. The need for better salvage treatment underlines the importance of developing new regimens.

Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Doxorubicin; Female; Fluoxymesterone; Humans; Logistic Models; Middle Aged; Mitolactol; Neoplasm Metastasis; Remission Induction; Survival Analysis; Tamoxifen; Treatment Outcome; Vincristine

Ninety-seven eligible and evaluable women with metastatic breast cancer were placed on a prospective clinical protocol to evaluate the use of continuous cyclic therapy with dibromodulcitol, doxorubicin, vincristine, tamoxifen, and fluoxymesterone (DAVTH) v DAVTH alternating with cyclophosphamide, methotrexate, 5-fluorouracil, and prednisone (CMFP); and the use of pretreatment and serial carcinoembryonic antigen (CEA) levels in these patients. Continuous DAVTH and DAVTH/CMFP were equivalent therapies with respect to response rates, time to treatment failure (TTF), and survival. Pretreatment CEA levels were elevated (greater than 5 ng/mL) in 42/97 patients and less than 5 ng/mL in the remaining patients. Patients with elevated pretreatment CEA levels were more likely to be estrogen receptor (ER) positive (P = .006), to have prolonged disease-free intervals (P = .017), to have hepatic (P = .004) and/or osseous (P = .01) metastases, and to have multiple sites of metastatic disease (P = .004). Pretreatment CEA levels did not significantly predict for overall response rates, TTF, or survival; nonetheless, those patients with low pretreatment CEA levels had more complete responses (CRs) (16/55 v 4/42; P = .02). Serial CEA levels during therapy revealed a number of interesting patterns. During the first 4 months of treatment, serial CEA levels in responding patients either (1) progressively declined (15/29 women with elevated pretreatment CEA levels), or (2) initially rose significantly (mean, 243% of pretreatment value) and then declined (14/29 women with elevated pretreatment CEA levels). Peak CEA levels in the latter patients were seen 27 to 135 days following initiation of cytotoxic therapy. In some patients the initial increase in the CEA level was incorrectly interpreted as evidence of impending disease progression. CEA levels frequently increased around the time of clinical disease progression. However, rising CEA levels rarely provided a clinically meaningful lead time before the appearance of other clinical evidence of disease progression. These data suggest that routine pretreatment and monthly serial CEA levels in metastatic breast cancer patients have minimal use in clinical practice. Two further noteworthy findings were observed in this prospective study. First, patients with an unknown ER status had a prolonged median survival when compared with patients with ER positive or negative tumors; this appeared to be related to prolonged disease-free inter

Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Carcinoembryonic Antigen; Clinical Laboratory Techniques; Clinical Trials as Topic; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Female; Fluorouracil; Fluoxymesterone; Follow-Up Studies; Humans; Methotrexate; Mitolactol; Neoplasm Metastasis; Prednisone; Prognosis; Prospective Studies; Random Allocation; Tamoxifen; Vincristine

The therapeutic effectiveness of combining tamoxifen with a combination chemotherapy regimen was tested in 135 patients with advanced breast cancer previously treated with chemotherapy. Patients were randomly allocated to received dibromodulcitol + Adriamycin (DA, 55 patients) or DA + tamoxifen (DAT, 67 patients). An additional 13 patients less than 50 years of age were assigned to DAT (DATN). Pretreatment characteristics were similar across both regimens. DAT and DATN yielded similar results in the less than 50-year-old cohort. DAT tended to be superior to DA with respect to response rate (55% versus 36%, p = 0.004), time to treatment failure (medians: 170 days versus 110 days, log rank p = 0.001), responders' time to treatment failure (360 days versus 220 days, p = 0.035), and survival (340 days versus 270 days, p = 0.18). Toxicity was similar in both regimens. Thus, addition of tamoxifen to a second-line DA regimen appears to increase the therapeutic effectiveness. It is suggested that the addition of this antiestrogen to other chemotherapy regimens would also be beneficial.

Topics: Adult; Aged; Antineoplastic Agents; Breast Neoplasms; Digestive System; Doxorubicin; Drug Therapy, Combination; Female; Humans; Middle Aged; Mitolactol; Neoplasm Metastasis; Prospective Studies; Random Allocation; Tamoxifen

A total of 268 patients with metastatic breast cancer were prospectively randomized to receive Adriamycin-vincristine (AV) alone, AV plus dibromodulcitol (AVD), or AV plus ICRF-159 (AVI). Two hundred thirty were eligible and had received prior chemotherapy. The objective response rates were 27%, 23%, and 16% for AV, AVD and AVI, respectively, and an additional 44% had stabilization of disease. Duration of responses ranged from 4.1 to 4.6 months and the times to treatment failure from 2.9 to 3.8 months. Median survivals ranged from 7.1 to 8.3 months. Performance status and the presence of liver or brain metastases were significant prognostic variables for outcome. These studies show that AVI is inferior to AV with respect to survival when prognostic variables are taken into account in a multivariate model, whereas AVD which utilizes a lower dose of Adriamycin appears to have comparable antitumor activity to AV. This does not appear to offer any benefit to patients previously treated with chemotherapy, as in this trial, but it may be an advantage to previously untreated patients since Adriamycin can be administered to responding patients over a longer period of time before an unacceptable total cumulative dose is reached.

Topics: Aged; Breast Neoplasms; Clinical Trials as Topic; Doxorubicin; Drug Therapy, Combination; Female; Humans; Menopause; Middle Aged; Mitolactol; Neoplasm Metastasis; Piperazines; Razoxane; Time Factors; Vincristine

Topics: Adult; Aged; Altretamine; Breast Neoplasms; Clinical Trials as Topic; Drug Evaluation; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Mitolactol; Neoplasm Metastasis; Time Factors; Triazines

The efficacy and modes of action of dibromodulcitol (DBD) and cisplatin (CDDP) were studied in several model systems. Combination treatments produced a longer survival time in mice bearing P388 solid lymphomas than either of the drugs alone. In the human metastatic melanoma HT-168 xenograft model the combined application of DBD and CDDP was also very effective, inducing a reduction in the number and volume of metastatic nodules. For V79 spheroids, DBD was mainly cytotoxic against the internal, quiescent cells, whereas cisplatin primarily killed cells in the proliferating, external regions of the spheroids. When combined, the drugs appeared to act synergistically throughout the spheroids. Studies on plasmid DNA showed that CDDP primarily generates cross-links, whereas single-strand breaks were dominant after DBD treatment. Upon using an assay for cleavage by restriction nuclease, antagonistic action of DBD and CDDP in combination may occur, nevertheless more strand breaks were always observed in these samples. These results suggest that the efficacy of combined DBD and CDDP is in part a result of 'spatial cooperation' by the drugs (i.e. affecting different cells) and in part the result of DNA damage produced by the combination treatments.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Body Weight; Cisplatin; DNA Damage; DNA, Neoplasm; Drug Screening Assays, Antitumor; Drug Synergism; Leukemia P388; Male; Melanoma; Mice; Mice, Inbred C57BL; Mice, Inbred CBA; Mice, Inbred DBA; Mitolactol; Neoplasm Metastasis; Neoplasm Transplantation; Tumor Cells, Cultured

A novel anthracycline antibiotic, siwenmycin, isolated from the culture of Streptomyces galilaeus var. siwenesis, was examined for its antitumor activities against P388, K562, B16-F10, HeLa, HEp-2 and Lewis lung carcinoma cell lines. The results showed that siwenmycin was effective against P388, K562, HeLa and HEp-2 tumor cell lines in vitro, and significantly inhibited the growth of the Lewis lung carcinoma cell line in vivo. Siwenmycin could also suppress spontaneous and artificial pulmonary metastases of B16-F10 and Lewis lung carcinoma cell lines in C57BL/6 mice. The inhibitory effect of siwenmycin on spontaneous pulmonary metastasis of Lewis lung carcinoma in C57BL/6 mice was even stronger than that of adriamycin (ADM), which is, at present, commonly used in clinical practice. Furthermore, the double-labeling test used in this study has verified that siwenmycin can inhibit cellular RNA synthesis at about one tenth the concentration required to inhibit DNA synthesis to the same degree, indicating that the antitumor mechanism of siwenmycin also differs from that of ADM. The acute toxicity of siwenmycin was very low, and it was as effective in vivo as in vitro, suggesting that this newly found antibiotic should be studied for possible clinical antitumor applications.

Topics: Aclarubicin; Animals; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; DNA, Neoplasm; Doxorubicin; HeLa Cells; Humans; Injections, Intraperitoneal; Lung Neoplasms; Melanoma, Experimental; Mice; Mice, Inbred Strains; Mitolactol; Mitomycins; Neoplasm Metastasis; RNA, Neoplasm; Tumor Cells, Cultured

Acute non-lymphatic leukaemia and myelodysplasia occur in a larger percentage of patients treated with dibromodulcitol (DBD) than in patients treated with other cytostatics. Sister chromatid exchanges (SCE) in the lymphocytes in peripheral blood as well as other haematological parameters were measured in women with breast cancer to investigate whether women who had previously been treated with DBD as a part of their treatment regime had an increased frequency of SCE or another haematological abnormality attributable to DBD. SCE levels were elevated in women treated with DBD as well as in those treated with other cytostatics compared to the untreated control group. All other haematological parameters were normal. There was no significant difference in the number of SCEs between the patients who received DBD and those treated with other cytostatics. The increased frequencies of SCE in the treated patients are attributable to various cytostatic agents, and there is no significant permanent increase in the frequency of SCE after exposure to DBD.

Topics: Breast Neoplasms; Female; Humans; Lymphocytes; Mitolactol; Neoplasm Metastasis; Sister Chromatid Exchange

A combined clinical and pharmacokinetic phase I study of the substituted hexitol dibromodulcitol (DBD), administered as a single oral monthly dose, has been performed. Twenty-three patients with advanced neoplasms received DBD doses ranging from 600 to 1,800 mg/m2 body surface area (BSA). The dose-limiting toxicity was myelosuppression, with both significant granulocytopenia and thrombocytopenia occurring at dose levels of 1,500 to 1,800 mg/m2. The average pharmacokinetic parameters for DBD, calculated on the basis of a one-compartment model with first-order absorption and elimination, include the elimination constant, .005 +/- .002/min; absorption constant, .012 +/- .009/min; and an apparent volume of distribution, 1.03 +/- .4 L/kg. The area under the drug concentration curve (AUC) and the peak drug level (Cmax) were linearly related to the dose administered (P less than .001). The mean AUC was 18.7 +/- 6.1 mmol/L min, and the mean Cmax was 47.1 +/- 16.8 mumol/L when normalized to a DBD dose of 1 gm/m2. The elimination constant was significantly reduced in patients with abnormal hepatic function (P less than .01). The elimination constant was not correlated with renal function. The half-life of DBD in plasma (158 minutes) was considerably shorter than the four-to eight-hour half-life of total radioactivity in plasma measured by previous investigators following the administration of radiolabeled DBD.

Topics: Absorption; Administration, Oral; Adult; Aged; Bone Marrow Transplantation; Carcinoma; Dianhydrogalactitol; Dose-Response Relationship, Drug; Drug Evaluation; Female; Half-Life; Humans; Kinetics; Male; Melanoma; Middle Aged; Mitolactol; Neoplasm Metastasis; Sarcoma; Time Factors

Twenty-three patients with metastatic breast carcinoma were induced with a complex systemic therapy regimen in an attempt to ascertain if a complete remission rate greater than 50% could be obtained with intensive drug exposure. The durability of the remissions was observed by discontinuing therapy after 3 cycles in complete remission or after 6 cycles of treatment, whichever was longer. In 13 patients consolidation radiation therapy to the pre-treatment sites of disease was administered after discontinuing systemic therapy. Each 28 day cycle of the drug regimen consisted of pulses of adriamycin, vincristine, dibromodulcitol, prednisone, methotrexate with leukovorin rescue, hexamethylmelamine, bleomycin (discontinued after entry #17), fluoxymesterone, and tamoxifen. Eighteen of the 23 patients achieved complete remissions (78%) and 3 had partial remissions. The median times to treatment failure and survival were, respectively, 12.3 and 19.4 mos. The times for complete remission patients were, respectively, 13.5 and 23.9 mos. Consolidation radiotherapy at greater than or equal to 40 Gy to drug induced pre-study sites of complete remission was associated with first relapses at pre-study sites in 5/30 (17%) instances, compared to 21/35 (60%) in sites not receiving radiotherapy. Side-effects were commensurate with the intensity of the treatment program and are detailed in the text. Although the achievement of a high complete remission rate is promising, the failure to extend their duration beyond that of historical data suggests that additional conceptual and therapeutic approaches need to be explored.

Topics: Altretamine; Antineoplastic Agents; Bleomycin; Breast Neoplasms; Combined Modality Therapy; Doxorubicin; Drug Administration Schedule; Female; Fluoxymesterone; Humans; Leucovorin; Leukopenia; Lung; Methotrexate; Mitolactol; Neoplasm Metastasis; Prednisone; Receptors, Estrogen; Tamoxifen; Thrombocytopenia; Time Factors; Vincristine

The Central Pennsylvania Oncology Group conducted a phase II study of mitolactol in advanced metastatic melanoma to determine the overall survival rate and duration of response to this agent. The starting dose was 100 mg/m2/day orally. If no hematologic toxicity was noted on weekly blood cell counts, the dose was increased to 130 mg/m2/day on Day 35, and, if still tolerated, to 160 mg/m2/day on Day 70. Six of 25 evaluable patients (24%) had objective partial response. The median duration of response was 20 weeks, with a range of 10-66 weeks. Six of 25 patients (24%) had stable measurable disease, with a median duration of 9 weeks. The median survival from date of entry in this study was 21 weeks in responding or stable patients compared to 7 weeks in nonresponders. Hematologic toxicity was the dose-limiting factor. This study shows that mitolactol has moderate activity against advanced melanoma, and the drug deserves further study in combination with nonmyelotoxic drugs.

Topics: Adult; Aged; Bone Marrow; Drug Evaluation; Female; Hemoglobins; Humans; Leukocyte Count; Male; Melanoma; Middle Aged; Mitolactol; Neoplasm Metastasis; Platelet Count

Topics: Adult; Aged; Drug Evaluation; Female; Humans; Male; Melanoma; Middle Aged; Mitolactol; Neoplasm Metastasis; Skin Neoplasms

Dibromodulcitol (DBD) and BCNU were administered to 20 patients with metastatic malignant melanoma who had not received prior chemotherapy. One complete and three partial responses were noted; duration of response was short. Dose limiting toxicity was thrombocytopenia. DBD and BCNU do not appear to improve response over single agent therapy for disseminated melanoma.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Drug Evaluation; Female; Humans; Male; Melanoma; Middle Aged; Mitolactol; Neoplasm Metastasis; Skin Neoplasms

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cisplatin; Dacarbazine; Drug Administration Schedule; Drug Evaluation; Female; Humans; Male; Melanoma; Middle Aged; Mitolactol; Neoplasm Metastasis; Vinblastine

Thirty-eight evaluable patients with metastatic breast cancer refractory to hormonal therapy and multiple chemotherapy regimens were treated with mitolactol at a dose of 130 mg/m2/day orally for 10 days every 6 weeks. Only one patient, with nodal and chest wall metastases, had a sustained complete regression; two patients had stable disease; and 35 patients had disease progression. The toxicity, which was primarily hematologic, was acceptable.

Topics: Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cyclophosphamide; Drug Evaluation; Female; Fluorouracil; Humans; Methotrexate; Middle Aged; Mitolactol; Neoplasm Metastasis; Receptors, Estrogen

Topics: Adult; Aged; Drug Evaluation; Female; Humans; Male; Melanoma; Middle Aged; Mitolactol; Neoplasm Metastasis

Twenty-six patients with disseminated malignant melanoma received an oral regimen of mitolactol and semustine (methyl-CCNU). Sixteen patients had received prior systemic therapy, and 16 had visceral involvement. There were no objective regressions among ten patients receiving the drugs as initial systemic therapy. However, one of 16 patients having prior systemic treatment did have an objective response. Hematologic and gastrointestinal toxic effects were well-tolerated.

Topics: Aged; Drug Evaluation; Drug Therapy, Combination; Female; Humans; Leukocyte Count; Leukopenia; Male; Melanoma; Middle Aged; Mitolactol; Neoplasm Metastasis; Nitrosourea Compounds; Pilot Projects; Platelet Count; Semustine; Skin Neoplasms; Thrombocytopenia

Hemangiopericytoma is an uncommon sarcoma arising from the pericapillary cells. While the rarity of this lesion precludes randomized investigation, metastatic hemangiopericytoma has been noted to respond to a variety of agents, including vincristine, adriamycin, actinomycin, and high-dose methotrexate. We wish to report an unusual case of this disease which failed to respond to the above but then exhibited a marked response to dibromodulcitol. In light of the unusual nature of this response, we would like to suggest a controlled trial of the use of dibromodulcitol in patients with this rare tumor.

Topics: Aged; Female; Hemangiopericytoma; Humans; Lung Neoplasms; Mitolactol; Neoplasm Metastasis; Thigh

Twenty-five patients with measurable metastatic melanoma refractory to DTIC and a nitrosourea were treated with dibromodulcitol (DBD). DBD was administered orally at bedtime at a dose of 100 mg/m2/day until hematologic toxicity (a greater than or equal to 50% decrease in the wbc or platelet count) was induced. Five patients experienced clinically useful objective remissions; responding lesions included both soft tissue metastases and visceral metastatic disease. It is concluded that DBD is useful in the treatment of patients with metastatic melanoma and thus joins DTIC and the nitrosoureas as single agents which are active against this malignancy.

Topics: Adult; Aged; Bone Marrow; Dacarbazine; Drug Evaluation; Drug Resistance; Female; Humans; Male; Melanoma; Middle Aged; Mitolactol; Neoplasm Metastasis; Nitrosourea Compounds; Remission, Spontaneous; Triazenes

A phase 1 to 2 evaluation of a combination of adriamycin (ADR) and dibromodulcitol (DBD) was performed in patients with progressive, metastatic breast carcinoma. All but one patient had been treated previously with chemotherapy. ADR was given on Day 1 or Days 1 and 8, and DBD was given on Days 1 to 10 of each 21- to 28-day treatment cycle. Side effects were evaluable in 54 patients, and 50 patients were evaluable for therapeutic response. The dose-limiting toxicities were leukopenia and thrombocytopenia. The severity of both toxicities increased as both the ADR and DBD doses increased; however, the effect of increases in DBD dose was much more profound. The mean white blood cell count and platelet nadirs occurred, respectively, on Days 15.3 and 15.9; both nadirs were delayed for 0.6 day by each 30-mg/sq m/day increase in the DBD dose and delayed for 1.7 to 3.9 days using the Day 1, 8 rather than the Day 1 ADR schedule Recovery of the peripheral counts by Day 29 was prolonged by the Day 1, 8 ADR schedule and by increasing the DBD dose. A tolerable dose schedule for previously treated patients was considered to be ADR, 40 mg/sq m on Day 1, and DBD, 135 mg/sq m on Days 1 to 10 repeated every 28 days. Responses were observed in 46% (23 of 50) of the patients. There were 1 complete remission, 19 partial remissions, and 3 improvements. Thirteen patients showed no change and 14 developed progressive disease. There were responses in 13 of 37 (36%) with visceral dominant disease as compared to 7 of 8 (87%) with osseous and 3 of 5 (60%) with soft tissue-dominant disease. There were 22 of 48 (46%) responses in patients previously exposed to alkylating agent therapy. Twnety-two patients had responded and 19 had failed to respond to prior alkylating agent-containing regimens; the response rates to DBD in these groups were respectively, 45 and 42%. The median time to remission was 29 days. The median time to therapeutic failure was 5.1 months for responders, 2.3 months for patients with no change, and 29 days for progressors. The combination of ADR and DBD appears to be an active and well-tolerated program in patients with previously treated metastatic breast carcinoma.

Topics: Adult; Aged; Breast Neoplasms; Doxorubicin; Drug Administration Schedule; Drug Evaluation; Drug Therapy, Combination; Female; Humans; Leukopenia; Middle Aged; Mitolactol; Neoplasm Metastasis; Remission, Spontaneous; Thrombocytopenia; Time Factors

Adriamycin is a new anticancer antibiotic with a wide spectrum of activity against solid tumours. The results obtained with this agent in 159 patients with histologically confirmed advanced metastastic malignancies are reported. Encouraging results were obtained in patients with sarcomas of bone and soft tissue (12/22). Response was also seen in mesothelioma (3/9) and lung cancer (5/15). A variety of other neoplasms was also treated and results obtained in neuroblastoma, testicular tumours, stomach carcinoma, breast cancer and nephroblastoma are reported. Treatment is discussed, with reference to response rates and toxicity. Results in 72 patients with advanced breast cancer, who received adriamycin in combination with other chemotherapeutic agents, are presented. Seventeen patients with primary liver cancer were also treated with adriamycin. To date, this is the only chemotherapeutic agent that appears to significantly improve survival times in patients with this resistant form of cancer. The prophylactic use of adriamycin against osteogenic sarcoma is also discussed.

Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Cyclophosphamide; Doxorubicin; Drug Therapy, Combination; Female; Fluorouracil; Humans; Infant; Liver Neoplasms; Lung Neoplasms; Male; Mesothelioma; Middle Aged; Mitolactol; Neoplasm Metastasis; Neoplasms; Pleural Neoplasms; Sarcoma

In studies on a model of induced pulmonary metastasis in mice a tumour host system was analysed which was not affected by immunogenicity of the tumour for the host; neither intensive immunosuppression nor immunization caused a significant change in the quantity of pulmonary metastatic nodules. In contrast the application of cytostatic drugs and of Corynebacterium parvum could modify the pulmonary resistance to the formation of tumour nodules by a factor greater than 100 in either direction. This finding confirms the observation of others that major modification of the resistance to metastatic tumour formation can occur independently of classical immunological mechanisms. Special attention is drawn to the fact that cyclophosphamide enhances the formation of metastatic nodules in this model by factors of 100 to more than 1,000 whereas other cytostatic drugs including the cyclophosphamide congeners iphosphamide and trophosphamide are active only factors between 2 and 12. The possible practical significance of these findings is discussed.

Topics: Alkylating Agents; Animals; Antineoplastic Agents; Busulfan; Cell Transformation, Neoplastic; Globulins; Horses; Immunosuppression Therapy; Lung; Lung Neoplasms; Lymph Nodes; Male; Mice; Mice, Inbred Strains; Mitolactol; Neoplasm Metastasis; Neoplasm Transplantation; Nitrogen Mustard Compounds; Osteosarcoma; Propionibacterium acnes; Radiation Effects; Sarcoma, Experimental

Topics: Acute Disease; Central Nervous System Diseases; Cytarabine; Humans; Injections, Spinal; Leukemia; Meninges; Methotrexate; Mitolactol; Neoplasm Metastasis; Nitrosourea Compounds; Pyrimethamine; Radiotherapy