The antiemetic activity of high-dose alizapride and high-dose metoclopramide in patients receiving cancer chemotherapy: a prospective, randomized, double-blind trial.

Alizapride is a new substituted benzamide with suggested superior antiemetic efficacy to and fewer side effects than metoclopramide. High-dose alizapride (4 mg/kg X five doses) was compared with high-dose metoclopramide (2 mg/kg X five doses) in a prospective, randomized, double-blind trial in 62 evaluable patients undergoing strongly emetic cancer chemotherapy. Patients receiving metoclopramide experienced significantly fewer vomiting episodes than patients receiving alizapride (median of three episodes vs. eight episodes; P less than 0.001). Metoclopramide was more effective in decreasing the volume of emesis than was alizapride (median of 100 ml vs. 360 ml; P less than 0.02). Seventy-two percent of the patients receiving alizapride and 57% of those receiving metoclopramide experienced side effects. High-dose metoclopramide is an effective antiemetic in patients receiving cancer chemotherapy. Alizapride is less effective and has more side effects than metoclopramide. We do not recommend the further use of alizapride.

Phase II study of doxifluridine in advanced colorectal adenocarcinoma.

Doxifluridine, a new fluoropyrimidine derivative, was tested in a cooperative phase II trial by the Swiss Group for Clinical Cancer Research in advanced measurable colorectal cancer. The drug was given in a five consecutive day schedule by a bolus intravenous injection at a dose of 4 g/m2 per day and repeated every three to four weeks. Of 42 eligible patients, 40 had no previous chemotherapy. Response was defined in 27 patients having received two or more courses of doxifluridine. Seven responses (26%) were observed. Responses were seen only in sigmoid and rectum primary tumors. Toxicity consisted mainly of leukopenia (53% of the evaluable patients), nausea and vomiting (38%). Other toxicities such as dermatitis, myocardial injury, and hair loss were also observed. Doxifluridine has therapeutic activity, albeit limited, in advanced rectosigmoid adenocarcinoma.

An evaluation of tamoxifen dose escalation in advanced breast cancer.

We escalated the dose of tamoxifen (TAM) to 30 or 40 mg daily in 23 patients who had experienced remission or stable disease (NC) under prior treatment with TAM 20 mg daily. One patient, whose bone and soft tissue disease had previously been stabilized under TAM 20 mg daily for 13 months, showed a partial remission (PR) lasting for 6 months. In 14 patients (64%) the disease remained stable for a median duration of 6 months (1.5-18+ mos.). Subjective improvement was noted in nine patients (39%), including the patient with PR and another one with progressive disease (PD). We conclude that dose escalation has no relevant activity in patients failing prior treatment with conventional doses of TAM.

Combination hormonotherapy with tamoxifen and fluoxymesterone in patients with advanced breast cancer relapsing on hormonotherapy.

33 patients were treated with a combination of tamoxifen and fluoxymesterone (10 mg t.i.d. each) after progression on prior hormonotherapy (HT). 6 of 22 patients (27%) exhibiting a partial response (PR) or stable disease (NC) on previous HT responded to the combination (median time to relapse 7 months, range 3.5 to 17+ months). 11 (50%) maintained NC (median duration 5 months, range 2% to 9.5 months). No response has been seen in 11 patients who experienced progressive disease during prior hormonal manipulation or who were not evaluable for response to prior HT. The overall response rate was 18% for the patient population as a whole (responders and nonresponders to previous HT), which most probably would be similar to the response rate if these patients received only fluoxymesterone.

[Posttraumatic soft tissue sarcoma: a case study of a malignant fibrous histiocytoma of the elbow joint which appeared six and a half years after a severe injury]. / Posttraumatisches Weichteilsarkom: Ein Fall eines malignen fibrösen Histiozytoms 6 3/4 Jahre nach einer Ellenbogenkontusion.

A 25-year-old patient was treated for a malignant fibrous histiocytoma of the elbow which appeared 6 3/4 years after a severe injury at this site. The reasons for assumption of a causal relationship between the trauma and tumor development are discussed.

[Phase-II-study with vindesine (desacetyl-vinblastine-amide-sulfate) in advanced malignant diseases]. / Phase-II-Studie mit Vindesine (Desacetyl-Vinblastin-Amid-Sulfat) bei fortgeschrittenen malignen Erkrankungen.

53 patients with advanced and measurable cancerr were treated with vindesine in doses of 3 mg/m2 (pretreated) and 4 mg/m2 (non pretreated) i.v. once weekly. 48 patients are evaluable for response: of 14 patients with squamous cell carcinoma of the lung, 1 partial remission (PR), 1 minor response (MR) and 1 no change (NC) were observed. In 5 patients with large cell carcinoma of the lung: 1 NC. In 3 with adenocarcinoma of the lung: 1 MR. One patient with nasopharyngeal carcinoma had progressive disease. Stable disease was observed in a patient with carcinoma of the tongue and in a patient with adenocarcinoma of the esophagus. Four patients with colorectal carcinoma had progressive disease. One MR was observed in a patient with breast cancer, while all of the other 3 patients had progressive disease. One carcinoma of the penis was stable. One MR was observed in a patient with Hodgkin's disease. One PR was observed in a case with no-Hodgkin's lymphoma. A patient with acute leukemia had progressive disease. Among 9 patients with malignant melanoma, 3 had an MR and 1 patient had stable disease. A patient with fibrosarcoma had progressive disease. Observed toxicity included leukopenia, thrombocytopenia, anemia, paresthesias, constipation, jaw pain, nausea, stomatitis, alopecia, loss of taste, pruritus and skin rash, weakness and fatigue.

Combination chemotherapy with VM-26, adriamycin bleomycin, and prednisone as a secondary treatment of malignant lymphoma.

Thirty-eight pretreated patients with Hodgkin's disease (HD) and malignant non-Hodgkin's lymphoma were given combination chemotherapy with VM-26, Adriamycin, bleomycin, and prednisone. Four of 15 evaluable patients with HD achieved a partial remission (PR), with a median duration of 8 months. Of 12 patients with diffuse poorly differentiated lymphocytic lymphoma, one achieved a complete remission (30+ months) and five achieved a PR (median, 6 months). One of three patients with histiocytic lymphoma had a PR of 1.5 months. There was one drug-related death. Five patients developed life-threatening hematologic toxicity. Two HD responders died of acute nonlymphocytic leukemia.

[Therapeutic results using VP 16-213 alone or in combination with 5-fluorouracil in liver cancer (hepatoma)]. / Therapieresultate mit VP 16-213 allein oder kombiniert mit 5-Fluorouracil beim Leberzellkarzinom (Hepatom).

The podophyllotoxin derivative VP 16-213 was used as monotherapy in 6 patients and combined with 5-fluorouracil in another 6. Of the 12 patients treated, 11 had measurable tumor criteria and 5 of these responded to treatment. These responses were attributed mainly to the effects of VP 16-213. Patients responding to chemotherapy lived significantly longer than non-responders. Each case of objective tumor response was accompanied by subjective improvement. In view of these results, a more active approach to the treatment of hepatocellular carcinoma would seem to be justified.

[VP 16-213 in combination with endoxan, methotrexate and oncovin as polychemotherapy for bronchogenic carcinoma]. / VP 16-213 in Kombination mit Endoxan, Methotrexat und Onconvin als Polychemotherapie beim Bronchuskarzinom

Thirty patients with bronchogenic carcinoma underwent an 8 week course of induction therapy consisting of cyclophosphamide, methotrexate, vincristine, and VP 16-213 (NSC 141 540). Those who achieved objective remission or tumor stabilization were then placed on an intermittent treatment schedule with the same drugs. Of the 30 patients, 17 had an objective response, 5 were unchanged and 8 progressed. Responses were more frequent in anaplastic carcinoma (13/19) than epidermoid or adenocarcinoma (4/11). The toxicity mainly consisted of leukopenia, thrombopenia, alopecia, nausea and vomiting. The implications of these findings in the planning of further chemotherapeutic programs are discussed.

A combination of cyclophosphamide, methotrexate, vincristine and VP 16-213 (NSC 141 540) in the treatment of bronchogenic carcinoma.

Thirty patients with bronchogenic carcinoma were treated with an 8-week induction therapy consisting of cyclophosphamide, methotrexate, vincristine and VP 16-213 (NSC 141 540). Those who achieved objective remission of tumor stabilization were then placed on an intermittent treatment schedule with the same drugs. Of the 30 patients, 17 had an objective response, 5 remained without change, and 8 progressed. Responses were more frequent among anaplastic (13/19) than epidermoid or adenocarcinoma (4/11). The toxicity consisted mainly of leucopenia, thrombopenia, alopecia, nausea and vomiting. The implications of these findings in the planning of further chemotherapeutic programs are discussed.

[First therapeutic experience with cis-platinum(II)diamindichloride (NSC 119875) in metastasizing ovarian and testicular carcinoma]. / Erste therapeutische Erfahrungen mit cis-Platinum(II)diamindichlorid (NSC 119875) bei metastasierenden Ovar- und Hodenkarzinomen

Ten patients with metastatic testicular or ovarian carcinoma were treated with cis-platinum II diaminedichloride. All had received prior chemotherapy with other agents. A therapeutic effect was seen in 7 cases, though it was of short duration in all instances. The drug proved to be very nephrotoxic and caused marked bone marrow depression. The future of this highly effective cytostatic agent, either with different dosage schedules or in combination with other drugs, is discussed. The possibility of new platinum derivatives with a better therapeutic index is also mentioned.

[Initial results with a epipodophyllotoxin derivative VP 16-213 in the treatment of acute leukemia]. / Erste Resultate mit dem Epipodophyllotoxin-Derivat VP 16-213 bei der Behandlung akuter Leukämien

Ten acute leukemia patients were treated with the new cytostatic agent VP 16-213. Almost all these patients had received previous therapy. One complete and two partial remissions were achieved, while one patient showed brief clinical improvement. VP 16-213 appears to be effective not only in acute monocytic leukemia, as therapeutic effects could also be observed in other forms of acute leukemia. VP 16-213 should further be tested in therapy of refractory acute leukemia patients as a drug of second choice. The relatively mild toxic effect of this substance and its special mode of action would appear to make it highly suitable for incorporation into combination chemotherapy regimes and further clinical trials.