Delta-9-tetrahydrocannabinol (THC) is an effective antiemetic as compared with placebos in patients receiving chemotherapy for cancer. In this study we compared THC with prochlorperazine (compazine) in a randomized, double-blind, crossover trial with patients who had failed to benefit from standard antiemetic therapy. Regardless of the emetic activity of the chemotherapeutic agents, there were more complete responses to THC courses (in 36 of 79 courses) than to prochlorperazine (in 16 of 78 courses). Of 25 patients who were treated with both drugs and who expressed a preference, 20 preferred THC (P = 0.005). Among patients under 20 years of age there was a higher proportion of complete responses to THC courses (15 of 20) than among older patients (21 of 59 courses; P = 0.004). Increased food intake occurred more frequently with THC (P = 0.008) and was associated with the presence of a "high." Of 36 THC courses resulting in complete antiemetic responses, 32 were associated with a high. We conclude that THC is an effective antiemetic in many patients who receive chemotherapy for cancer and for whom other antiemetics are ineffective. (N Engl J Med 302:135--138, 1980).

Forty-one patients with advanced squamous cell lung cancer and no prior chemotherapy were entered in a prospectively randomized trial comparing dianhydrogalactitol plus Adriamycin (DA) versus DA plus cis-dichlorodiammineplatinum(II) (DAP). The DAP regimen was superior to the DA regimen in regression rate (53% versus 27%), median regression duration (255 versus 122 days), median time to tumor progression (approximately 175 versus 58 days), and median survival time (185 versus 126 days). Patients who were greater than 60 years old responded particularly well to the DAP regimen and accounted for most of the survival advantage. Nausea, vomiting, and myelosuppression were more frequent and severe with the DAP regimen. This study seems to indicate a role of cis-dichlorodiammineplatinum(II) in patients with advanced squamous cell lung cancer. The particular advantage noted for older patients needs further evaluation.

Moderate doses of methotrexate and L-asparaginase were added to standard doses fo 5-fluorouracil, Adriamycin, and cyclophosphamide in an attempt to improve the overall response rate and survival following chemotherapy. In addition, nonspecific immunotherapy with either Corynebacterium parvum or Pseudomonas vaccine was integrated into this prospective randomized clinical trial. The overall toxicity (degree of granulocytopenia and thrombocytopenia, length of myelosuppression, and incidence of myelosuppression-related infection and infectious deaths) increased considerably and led to the termination of patient accrual. The incidence of stomatitis and diarrhea was also increased with the addition of methotrexate and L-asparaginase, and apparently was potentiated by the addition of Pseudomonas vaccine to this five-drug combination.

This study compares two combinations of drugs with proven activity in gastrointestinal malignancy. The drugs utilized are 5-fluorouracil (5FU), mitomycin C (Mito C), and 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (MeCCNU). All 57 patients received 5FU 25 mg/kg as a 24-hour infusion for 5 days every 4 weeks. One group received Mito C 20 mg/m2 IV bolus every 8 weeks. The second group received MeCCNU 150 mg/m2 orally every 8 weeks. These combinations are tolerable, and the toxicities are acceptable. The response to 5FU/Mito C is more efficacious at 47% than 5FU/MeCCNU at 25% in the treatment of evaluable patients with colorectal malignancy.

Seventy patients with small-cell lung carcinoma limited to the thorax +/- ipsilateral supraclavicular lymph nodes were randomized to either of two study arms: 33 patients received radiation therapy (RT) alone consisting of 4500 rads in 5-6 weeks to primary tumor and regional lymph nodes, and 3500 rads in 2 1/2 weeks to brain as prophylaxis; 37 patients received, in addition to the RT above, chemotherapy (CT) with cyclophosphamide (500 mg/m2), Adriamycin (50 mg/m2), and DTIC (250 mg/m2) every 3 weeks given in two cycles before RT and seven cycles post-RT. Patients receiving RT alone who showed recurrence were crossed over to receive CT as above. Of 23 patients receiving RT alone who were evaluable 17 or 74% were responders; seven of these responses were complete (30%). On the RT and CT arm, of 24 evaluable cases, the response rate was 75%, of which 12 (50%) were complete. The median duration of disease-free survival of patients receiving RT + CT was 27 weeks, which ws superior to that of patients receiving RT alone (9.9 weeks, p = 0.019). The median survival of responders was essentially the same on both treatment arms; RT + CT, 47.7 weeks vs. RT alone, 50 weeks (p = N.S.).

Twenty-nine patients with advanced malignant melanoma were randomized to receive DTIC at a dose of 200 mg/m2 iv on Days 1-5 and cis-dichlorodiammine-platinum(II) at a dose of 40 mg/m2 iv on Days 1 and 4, repeated every 4 weeks (group A), or the same drugs plus procarbazine at a dose of 75 mg/m2 orally daily on Days 1-8 and vincristine at a dose of 1.4 mg/m2 iv on Day 1 (group B). These drugs were generally well-tolerated, but five of 16 patients in group A and six of 13 patients in group B required dose modification for either hematologic or renal toxicity. There were six objective responses among 16 patients in group A including one complete regression, while there were two objective responses among 13 patients in group B.

A randomized trial was conducted by the Southwest Oncology Group (SWOG) in advanced carcinoma of the stomach and pancreas. Patients were assigned to receive monthly 5-fluorouracil 96-hour continuous infusions with either bolus mitomycin-C or oral methyl-CCNU. Mitomycin-C and methyl-CCNU were administered every eight weeks. The 5 FU-mitomycin combination produced a 14% and 22% response rate in disseminated stomach and pancreatic carcinoma, respectively. The combination of infusion 5 FU and methyl-CCNU achieved responses in 9% and 5% of stomach and pancreatic tumors, respectively. There was no significant difference in survival between limbs for either tumor. Median survival in gastric carcinoma on the 5 FU-mitomycin regimen was 25 weeks vs. 18 weeks on the 5 FU-METHYL-CCNU arm. In pancreatic carcinoma median survival on the mitomycin limb was 19 weeks as compared to 17 weeks on the methyl-CCNU program. Leukopenia was greater for the first course on the mitomycin limb. Regression analysis demonstrated that performance status was the most important pretreatment characteristic for predicting survival in both tumors. Neither 5 FU infusion combination appears to significantly alter the dismal prognosis of advanced upper gastrointestinal neoplasms.

Twenty-five previously untreated patients with advanced testicular carcinoma were treated with a five-drug combination chemotherapy program containing cis-dichlorodiammineplatinum(II). This drug regimen was used as part of a trial testing the efficacy of cytoreductive surgery (15 patients) and in ten additional patients not eligible for the combined modality study. Eleven of 25 (44%) patients had a complete response and 11 of 25 (44%) patients had a partial response. Nine of 11 (82%) patients with minimal tumor burden upon initiation of chemotherapy had a complete response. With a median followup of 12+ months, none have relapsed. Complete remissions in patients with very advanced bulky disease were rare (two of 14 [14%] patients) and of short duration, with both patients relapsing. In addition to the usual hematologic toxicity, 14 of 25 (56%) patients developed hypomagnesemia and five of 25 (20%) patients developed systemic reactions to cis-dichlorodiammineplatinum(II) which prevented further drug administration.

Patients with metastatic nonseminomatous testicular cancer received an induction regimen consisting of bleomycin in 24-hour infusions and bolus iv doses of vinblastine followed by an Adriamycin and cis-dichlorodiammineplatinum(II) combination. Patients achieving complete remission after one or two cycles of this induction chemotherapy were then randomized to receive either radiotherapy (RT) to the previously involved tumor areas or maintenance chemotherapy (MCT) with CCNU, methotrexate, and vinblastine for 2 years. Among 62 evaluable patients, induction chemotherapy achieved 15 (24%) partial remissions and 35 (56%) complete remissions. Two patients with partial remission and single pulmonary metastases were rendered disease-free by surgical resection of residual tumor. Twenty patients received MCT and 15 received RT. To date, median survival is 10,8+ months in the MCT group with five relapses and 12.5 months in the RT group with two relapses. Toxicity in the induction phase was moderately severe with two drug-related deaths.

Two regimens of chemotherapy for metastatic breast cancer were compared in a randomized controlled fashion. Regimen 1 consisted of cyclophosphamide, vinblastine, methotrexate and 5-fluorouracil (CVMF). Regimen 2 consisted of cyclophosphamide, adriamycin, methotrexate and 5-fluorouracil (CAMF). The patient population consisted of both black and white postmenopausal females who had not received any prior chemotherapy. Objective responses were observed in 25/57 patients treated with CVMF and in 28/51 patients treated with CAMF. Neither race nor choice of chemotherapeutic regimen affected prognosis, although there were differences in the pattern of metastatic involvement between the two racial groups. The median duration of survival of patients who responded to therapy has not yet been reached but will be in excess of 12 months.

From June 1974 to October 1976, 288 patients with small cell undifferentiated lung carcinoma were entered into a randomized, controlled study comparing the two noncycle-active induction regimens of cyclophosphamide vs. the combination of cyclophosphamide, doxorubicin and imidazole carboximide (DTIC). Patients were stratified by extent of disease, previous radiotherapy and performance status. Responding patients and those who did not progress were then randomized to receive their initial regimen alone, or their initial regimen with added cycle-active therapy (vincristine, hydroxyurea and methotrexate). While only 4/34 (12%) evaluable patients treated with cyclophosphamide achieved a response (greater than 50% regression), a final total of 119/217 (57%) evaluable patients on the three drugs have responded (p = 0.005). The survival curve for all the combination-treated patients was significantly better than for those treated with cyclophosphamide alone (p = 0.012). There was no demonstrable statistical superiority in length of remission or survival for patients on the combination who received in addition cycle-active consolidation therapy. In the combination chemotherapy group, survival duration was longer for patients with limited disease than extensive disease (p = 0.035). There was a strong correlation between quality of remission produced by the combination and survival.

Two double-blind, crossover trials comparing the antiemetic effectiveness of nabilone, a new synthetic cannabinoid, with that of prochlorperazine were conducted in patients with severe nausea and vomiting associated with anticancer chemotherapy. Of 113 patients evaluated, 90 (80 per cent) responded to nabilone therapy, whereas only 36 (32 per cent) responded to prochlorperazine (P less than 0.001). Complete relief of symptoms was infrequent, occurring only in nine patients (8 per cent) given nabilone. When both drugs were compared, both nausea (P less than 0.01) and vomiting episodes (P less than 0.001) were significantly lower in patients given nabilone. Moreover, patients clearly favored nabilone for continued use (P less than 0.001). Predominant side effects noted by patients were similar for both agents and included somnolence, dry mouth and dizziness but were about twice as frequent and more often severe in patients receiving nabilone. In addition, four patients (3 per cent) taking nabilone had side effects (hallucinations in three, hypotension in one) that required medical attention. Euphoria associated with nabilone was infrequent (16 per cent) and mild.

Thirty-nine untreated patients with either lymphocytic or nodular mixed/nodular histiocytic non-Hodgkin's lymphoma, stage II--IV, were randomized to treatment with total body irradiation (TBI), 100 rads in 10 fractions over 12 days, plus combination chemotherapy with either cyclophosphamide, vincristine and prednisone (CVP) or cyclophosphamide, vincristine, procarbazine and prednisone (C-MOPP) or to treatment with combination chemotherapy (CVP or C-MOPP) alone. Remission rate and duration was comparable for both treatment groups; thus the use of both treatment modalities ab initio provides no therapeutic advantage.

One hundred fifty-seven premenopausal women with metastatic breast cancer were prospectively randomized to treatment consisting of oophorectomy + vincristine, prednisone, cyclophosphamide, methotrexate, 5-fluorouracil (VPCMF) (Reg. I) or oophorectomy + cyclophosphamide (Reg. II) or oophorectomy followed by an observation period (Phase 1), followed by VPCMF (Phase 2) (Reg. III). Complete plus partial response rates were 72% on Reg. I, 65% on Reg. II, 18% on Reg. III, Phase 1 and 50% on Reg. III, Phase 2. Median duration of response for Reg. I was 17 months, for Reg. II 16 months, and for Phase 1 and Phase 2 of Reg. III, respectively, 5 months and 8 months. The response rate for patients treated with oophorectomy plus chemotherapy is significantly higher than the response rate achieved with oophorectomy alone as first treatment following the appearance of metastases in premenopausal women.