To investigate the effects of concurrent administration of an anabolic steroid upon hematopoiesis and metabolism in patients with cancer who were receiving cytotoxic chemotherapy, a randomized trial was conducted. Thirty-three evaluable patients received intensive multiple-agent chemotherapy: 17 received in addition nandrolone decanoate ("Deca-Durabolin"), 200 mg intramuscularly each week. The nandrolone-treated patients showed significantly better maintenance of hemoglobin concentrations and body weight, and a highly significant reduction in number of blood transfusions. Improved survival in the androgen-treated patients did not achieve significance. There were no differences in neutrophil or platelet counts or in tolerance of cytotoxic drugs. Toxicity from nandrolone therapy was minimal.

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.

Sixty consecutive patients, 15-60 years old, with ANLL were divided randomly into three groups for induction treatment with one of the following regimens: R1, daunorubicin (DNR) 1.5 mg/kg on day 1 + ARA-C 2 mg/kg body weight on days 1-5; R2, DNR 1.5 mg/kg on days 1 and 2 + ARA-C 2 mg/kg on days 4-8; R3, DNR-DNA complex 1.5 mg/kg on days 1 and 2 + ARA-C 2 mg/kg on days 4-8. Maintenance treatment consisted of monthly courses of DNR 1.5 mg/kg (R1, R2) or DNR-DNA 1.5 mg/kg (R3) combined with ARA-C 1 mg/kg on days 1-5, alternating with thioguanine 2 mg/kg PO on days 1-5 combined with ARA-C 1 mg/kg IV on days 1-5. Fourteen patients of 20 went into complete remission with R1, 13 or 18 with R2, and 15 of 22 with R3. The overall remission frequency was 70% and there was no significant difference between the different groups. The median time in first remission and the median survival time were 300 and 510 days, respectively, with R1; 335 and 495 days with R2; and 295 and 677 days with R3. There was no statistically significant difference between the groups treated according to the different regimens concerning the time in first remission. Survival was slightly better with R3 than with R1. Treatment with the DNR-DNA complex caused less pronounced thrombocytopenia and fewer 'minor' cardiac abnormalities than treatment with free DNR in the same dosage schedule.

During the past 4 years, a sequential study was conducted to compare the effect of tamoxifen (TAM) alone and TAM plus 1-(2-tetrahydrofuryl)-5-fluorouracil (FT) in the treatment of advanced breast cancer. The overall response rates were 28.9% in 45 patients treated with TAM, and 43.2% in 37 treated with TAM + FT. In regard to dominant site of lesions, 4 out of 9 patients (44.4%) with visceral involvement responded to TAM + FT, whereas none out of 10 responded to TAM alone. In a crossover study, 4 out of 5 failures to TAM responded favorably to TAM + FT. The median value of survival was 24 months in patients treated with TAM alone and 36 months with TAM + FT. Side effects such as gastrointestinal disorders and bone marrow suppression slightly increased in incidence when cytotoxic chemotherapy was combined with TAM. The present chemo-endocrine regimen with TAM + FT showed some advantages over TAM alone.

Forty-nine patients with small cell bronchogenic carcinoma (23 limited and 26 extensive disease) received their first two of three courses of intensive remission induction chemotherapy with (21 patients) or without (28 patients) intravenous hyperalimentation (IVH). The chemotherapy included six remission induction courses with ECHO (epipodophyllotoxin VP-16-213, cyclophosphamide, hydroxydaunorubicin, oncovin), followed by six courses of maintenance with PRIME (procarbazine, ifosfamide, methotrexate). Prophylactic brain irradiation (3000 r/2 weeks) was given to all patients and those with limited disease received chest irradiation (5000 r/5 weeks) at the completion of ECHO. Thus far, all 30 patients who have completed three courses of ECHO have responded with complete (70% CR) or partial (30% PR) remissions. The CR rate was higher for patients receiving IVH (85% vs 59%, P = 0.25). Myelosuppression was pronounced and predominantly in the form of neutropenia. Median lowest neutrophil counts were zero during each of the three courses of ECHO and lasted a median of 5 days at levels less than 500/mm3. Major infections occurred in 21% of courses. The administration of IVH did not ameliorate the hematologic, gastrointestinal, and infectious morbidity of ECHO chemotherapy. However, it resulted in preservation of body weight (P less than 0.01) and improved skin reactivity to a battery of six skin antigens (P = 0.03). The administration of intensive therapy with ECHO +/- IVH was well tolerated and resulted in high CR rates in patients with small cell bronchogenic carcinoma. The administration of IVH was most helpful in preventing severe weight loss and augmenting response to a battery of skin antigens. The long term survival effects of these observations are yet to be determined.

Total parenteral nutrition (TPN) has been suggested as a useful addition to chemotherapy of malignant disease in the hope of decreasing drug toxicity and increasing drug tolerance. In this study, 17 of 36 patients given chemotherapy for advanced diffuse lymphoma were randomly selected to receive TPN. The dose of the chemotherapeutic agents to be administered was decreased according to predetermined toxicity guidelines. A comparison of drug dosage in the group receiving TPN and the group receiving standard nutrition is a measure of drug tolerance in these patients. Drug dosage was evaluable in 15 TPN and 18 standard nutrition patients. No difference in tolerance of any specific drug or total drug dose occurred when all patients in both groups were compared. Similar comparisons in subgroups of malnourished patients and responding patients also revealed no difference. A cycle-by-cycle analysis demonstrated no difference in any phase of therapy. The wbc count, platelet count, and albumin level, on the first day of each cycle, the nadir during cycles and the day of nadir were compared in TPN and standard nutrition patients. No differences were found. This study does not suggest improved drug tolerance in lymphoma patients as a result of TPN support. Further controlled studies are needed to determine which groups of cancer patients might benefit from TPN and how these benefits occur.

A randomized trial was initiated to compare the effects of PIVN-associated chemotherapy (adriamycin, vincristine, VP16-213 and cyclophosphamide) versus as chemotherapy control group in patients with small-cell lung neoplasias. The results obtained are preliminary. The test group included ten patients whereas nine were followed in the control group. PIVN was scheduled each day the patient underwent chemotherapy. Each patient received 1550 kcal/day, which included 10% glucose, 20% lipids, and amino acids which may or may not be mixed in the same infusion bottle. The results show three PIVN patients presently in complete remission at the end of three courses of treatment compared to two over the same time period in the chemotherapy control group. Of all patients who can be evaluated at this time, five out of six PIVN patients are in complete remission compared to four out of five in the control group. There was no significant difference in either general health or side effects, such as nausea and vomiting. The median length of time for which a low white cell or platelet count was noted was the same for both groups.

The anthracyclines, daunomycin and Adriamycin, have become two of the most important chemotherapeutic agents in the treatment of pediatric acute nonlymphocytic leukemia. Data are presented on 306 children treated after initial diagnosis with an anthracycline or one of the chemotherapeutic agents. The remission rate was 65%. When not used during maintenance therapy, the anthracyclines have been shown to be effective in inducing a second remission even though the drug was used during initial therapy. An ongoing randomized study utilizing Adriamycin in induction of remission and during maintenance therapy is also discussed.

In a trial of postoperative adjuvant chemotherapy women with primary breast cancer and spread to one or more axillary nodes were randomised to receive a six-month course of either the single agent chlorambucil or the five-drug combination of chlorambucil, methotrexate, fluorouracil, vincristine, and adriamycin. On completing the treatment 47 patients were asked to fill in questionnaires at home on the side effects of treatment and its influence on the quality of their life. Side effects including nausea, vomiting, malaise, and alopecia had been severe enough to interfere with their lifestyle in 9 (42%) of the patients who had received the single agent and 19 (79%) of those who had received multiple-drug treatment. Various other side effects were reported by a few patients. Seven (29%) of the patients who had received the multiple-drug schedule voluntarily added that the treatment had been "unbearable" or "could never be gone though again." The proportion of patients who had experienced severe side effects while receiving the treatment was considerable; hence such adjuvant chemotherapy is justifiable only if it will substantially improve a patient's prognosis.

Fifty-five patients harboring a variety of neoplasms and previously found to have severe nausea or emesis from antitumor drugs were given antiemetic prophylaxis in a double-blind, randomized, crossover fashion. Tetrahydrocannabinol (THC), prochlorperazine, and placebo were compared. Nausea was absent in 40 of 55 patients receiving THC, eight of 55 patients receiving prochlorperazine, and five of 55 in the placebo group. The antiemetic effect of THC appeared to be more efficacious for cyclophosphamide, fluorouracil, and doxorubicin hydrochloride, and less so for mechlorethamine hydrochloride and the nitrosureas. Tetrahydrocannabinol appears to offer significant control of nausea in most patients and exceeding by far that provided by prochlorperazine.

Seventy-eight patients with disseminated testicular cancer were entered on a random prospective study evaluating three separate remission induction arms. Therapy with cis-diamminedichloroplatinum (20 mg/M2 for five consecutive days every three weeks for 3-4 courses) and bleomycin (30 units intravenous push weekly for 12 consecutive weeks) was constant. Patients were allocated at random to one of the following induction regimens (in combination with platinum plus bleomycin): (1) vinblastine 0.4 mg/kg every three weeks for four courses; (2) vinblastine 0.3 mg/kg every three weeks for four courses; or (3) vinblastine 0.2 mg/kg plus Adriamycin 50 mg/M2 every three weeks for four courses. All patients received maintenance therapy with vinblastine 0.3 mg/kg once a month for 20 months (total therapy two years) unless progressive disease intervened. The incidence of granulocytopenic fever and sepsis was highest with regimen 1, as 9 patients (35%) developed granulocytopenic fever requiring hospitalization and antibiotics; only 4 (15%) patients on regimen 2 developed granulocytopenic fever. No patients on regimen 2 had documented sepsis. Fifty-three patients (68%) achieved complete remission and an additional 11 patients were rendered free of disease with surgical resection of residual localized disease. Fifty-three patients (68%) remain alive and continuously free of disease from 15+ to 39+ months. There was no difference in the complete remission rate or disease-free status with the higher dosage of vinblastine (regimen 1) during remission induction therapy compared to the less toxic lower dosage of vinblastine (regimen 2). This suggests that dosage reduction of vinblastine to 0.3 mg/kg can produce equivalent therapeutic results with diminished toxicity, and we no longer recommend the 0.4 mg/kg vinblastine dosage.

A total of 114 patients with bronchogenic small cell anaplastic carcinoma and staged as having regional disease all underwent combination chemotherapy consisting of CCNU, cyclophosphamide, and methotrexate. They were randomized to receive either radiotherapy to the primary tumor and regional lymph nodes (4000 rad) or extensive radiotherapy, which included the brain, adrenals, and upper retroperitoneal lymph nodes. Fifteen patients were free of disease after 18 months of chemotherapy and the treatment was discontinued. Only 3 patients subsequently relapsed. No difference was observed between the two groups of patients in median survival time, response rate, duration of response or relapse pattern, including the frequency of brain metastasis.

Eighty-four evaluable patients with advanced Hodgkin's disease (Stages IIB, IIIA age greater than 35 or mixed cellularity or lymphocyte depletion histology, IIIB, IVA, and IVB) were treated with alternating monthly MOPP and Adriamycin, bleomycin, dacarbazine, and vinblastine (ABDV). Radiation therapy (RT), 2000 rads in two weeks, was given to areas of initial bulky disease in untreated patients. Complete remission (CR) rates were 80% for previously untreated, 65% for prior RT or minimal chemotherapy treated, and 50% for heavily pretreated patients. Among 49 previously untreated patients there were no primary treatment failures. The estimated two-year relapse rate for the CR group was 9%. The therapeutic effectiveness of this program may have been due to either or both of the following elements: (1) two non-cross-resistant drug combinations, (2) low dose adjuvant RT to initial sites of bulky disease. These early results are among the best reported for the treatment of advanced Hodgkin's disease.

A double blind-cross-over randomised clinical trial has been conducted to compare the antiemetic effects of tetrahydrocannabinol, thiethylperazine and metoclopramide. There were no significant differences in the antiemetic effects of these drugs. The incidence of adverse reactions as recorded by both the staff and the patients was significantly higher in the tetrahydrocannabinol group than in either the metoclopramide or thiethylperazine groups. This trial has established that in the dosages used tetrahydrocannabinol given by mouth has an antiemetic effect of approximately the same order as thiethylperazine and metoclopramide. However, its adverse effects are sufficiently greater than those of the other agents to prevent is widespread usage for this purpose. Tetrahydrocannabinol taken by mouth is not recommended as a routine antiemetic agent in cancer chemotherapy.

To evaluate the efficacy of lithium carbonate in ameliorating leukopenia, 37 patients (3 to 26 years old, mea (less than or equal to 1,000/mm3) over 40% of the time were designated at random on the last day of 82 separate chemotherapy courses to receive lithium or no treatment. Four could not take the drug because of the size of the capsules. There were 39 controls and 39 patients given lithium. Blood levels were maintained at 0.2 to 1.2 mEq/1 (median 0.7). The median drop of WBC in the treated group was 3,400/mm3 with a nadir of 1,800/mm3 vs 5,000 and 1,400, respectively, for the untreated patients (P LESS THAN 0.01). Eight patients (21%) in the lithium-treated group became severly leukopenic (less than or equal to 1,000/mm3) while 14 (36%) in the control group became leukopenic to that extent. Twenty-four patient days were spent with the WBC less than or equal to 1,000/mm3 after lithium and 57 days in the control group. Three patients required admission for 24 hospital days for fever while leukopenic after lithium, whereas seven patients spent 62 days in the hospital in the control group. Lithium reduces the period of leukopenia after chemotherapy during which time the patients may acquire infections.

Sixty-nine postmenopausal patients with advanced breast cancer were randomized to receive treatment with cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) or CCNU, melphalan, methotrexate, and prednisone (CAMP). Response rate (partial and complete remission) was significantly higher with CMF (50%) than with CAMP (20%). Hematologic toxic effects were equally pronounced with the two combinations as were the other side effects with the exception of alopecia, which occurred most frequently with CMF.

From 1975 to 1978, 69 children with non-Hodgkin's lymphoma were staged and treated in a randomized protocol to determine the contribution of involved-field radiotherapy (IF-RT) to an effective drug regimen in Stages III-IV and the efficacy of prophylactic treatment of the central nervous system with cranial irradiation and intrathecal methotrexate in Stage II-IV. Induction therapy for Stages I-II was vincristine, prednisone, cyclophosphamide and IF-RT (3000-3500 rad). Stages III-IV received the same three drugs plus adriamycin, and were randomized to received or not receive IF-RT. The complete remission rate was 88%. After randomization to receive CNS prophylaxis or not, all children received oral mercaptopurine and methotrexate for 18 months. The two-year actuarial estimate of disease-free survival for all responders is 55% and is significantly influenced by stage. (Ninety percent disease-free survival for Stages I-II, versus 38.8% for III-IV, P less than .05). We observed no benefit but added toxicity from IF-RT in Stages III-IV. Efforts at CNS prophylaxis in high-risk children are warranted, since only 1 of 18 children randomized to receive prophylaxis developed CNS disease as the site of first relapse, whereas 4 of 16 receiving no prophylaxis did so.

The antiemetic effect of oral nabilone, a synthetic cannabinoid, given at a dose of 2 mg every 12 hours was compared to oral slow-release capsules of prochlorperazine given at a dose of 10 mg every 12 hours by a double-blind crossover method in 37 patients receiving cancer chemotherapy. Patients received one of the following as the primary emetic stimulus: high-dose cis-dichlorodiammineplatinum(II) (DDP), low-dose DDP, mechlorethamine, streptozotocin, actinomycin D, or DTIC. Although results varied according to strength of emetic stimulus received, both nabilone and prochlorperazine appeared to produce antiemetic effects. Eighteen of the 37 patients achieved a complete or partial elimination of symptoms: seven with nabilone alone, three with prochlorperazine alone, and eight with each drug. Nabilone appeared to be the more effective antiemetic for patients who received chemotherapy agents other than high dose DDP; it was equivalent to prochlorperazine for those who did receive high-dose DDP. Side effects from prochlorperazine were limited to mild drowsiness occurring among 35% of the patients. The side effects from nabilone were drowsiness and dizziness which occurred frequently and were dose-limiting in 25% of patients.