C. P. J. Vendrik

Combination Chemotherapy with Cisplatin and Methotrexate in Advanced Transitional Cell Cancer of the Bladder

We studied 53 patients with bidimensionally measurable metastases of transitional cell cancer of the bladder who were treated with a planned regimen of 70 mg. per m. cisplatin intravenously on day 1, and 40 mg. per m. methotrexate intravenously on days 8 and 15 every 3 weeks. The toxicity of this regimen, with agranulocytosis and mucositis as the most important side effects, was so severe that only 17 per cent of the patients actually received the protocol regimen without modification. Six patients were ineligible and 47 were evaluable for toxicity, including 43 who were evaluable for response. The response to treatment was assessed after each second treatment cycle. A complete response was achieved in 10 patients (23 per cent) and a partial response was achieved in 10 (23 per cent). The median duration of response was 64 weeks for patients with a complete response and 23 weeks for those with a partial response, while the median duration of survival was 81 and 37 weeks, respectively. The aforementioned regimen with allowance of routine leucovorin rescue is tested as preoperative chemotherapy in patients with stages T3 to T4 nonmetastatic bladder cancer.

Cyvadic in advanced soft tissue sarcoma: A randomized study comparing two schedules: A study of the EORTC soft tissue and bone sarcoma group

Two hundred forty‐six adults with advanced progressive soft tissue sarcoma received combination chemotherapy with cyclophosphamide, vincristine, Adriamycin (doxorubicin), and DTIC. They were randomly allocated to receive the four drugs simultaneously every 4 weeks (S1: CYVADIC), or pairs of drugs (S2: ADIC‐CYV) alternating at 4 weekly intervals. One hundred sixty‐two patients completed 8 weeks of chemotherapy, and were considered to be evaluable for response. There were 18 complete remissions and 25 partial remissions, an overall response rate of 26%, with a highly significant difference between the two arms in favor of S1 (38% versus 14%, P = 0.001). There were no significant differences between S1 and S2 in terms of median duration of remissions (62 versus 39 weeks), and median survival of responders (85 versus 80 weeks) and of all evaluable patients (43 versus 45 weeks). Karnofsky index (KI) was the single most important prognostic factor. Patients with KI 90–100 showed a remission rate of 41% (56% on the S1 regimen) in contrast with 14% in those with KI 50–80. No patient with a KI of 50 responded to chemotherapy. The main toxicities were nausea, vomiting, anorexia, alopecia and myelosuppression, but did not differ significantly between the two regimens. Our findings suggest that stratification according to KI is essential for studies on chemotherapy for advanced soft tissue sarcomas in order to make a valuable comparison of treatment results.

Five-year survival of patients with disseminated nonseminomatous testicular cancer treated with cisplatin, vinblastine, and bleomycin

Ninety‐one patients with disseminated testicular non‐seminomas were treated with 3 to 4 cycles of cisplatin, vinblastine, and bleomycin (PVB) induction chemotherapy followed by cisplatin and vinblastine maintenance therapy for 1 year. The follow‐up of these patients ranges from 24 to 66 months. Forty‐nine (54%) patients achieved complete remission by chemotherapy alone and 14 (15%) were rendered free of tumor by surgery after chemotherapy, for a total complete remission rate of 69%. Three complete responders relapsed within 13 months, and two died. One additional complete responder died of a non‐cancer‐related cause. One of the surgical complete responders relapsed and died. Overall, 58 (64%) patients remain free of disease. The 5‐year survival is 95% for complete responders, 32% for partial responders, and 72% overall. This combination regimen has significantly improved the survival of disseminated testicular cancer patients, equaling that of Stage II patients in older literature.

High-dose versus low-dose vinblastine in cisplatin-vinblastine-bleomycin combination chemotherapy of non-seminomatous testicular cancer: a randomized study of the EORTC Genitourinary Tract Cancer Cooperative Group.

Two hundred fourteen patients with disseminated non-seminomatous testicular cancer were randomized to receive induction chemotherapy with cisplatin, vinblastine, and bleomycin (PVB). The randomization was for vinblastine 0.4 mg/kg/cycle or 0.3 mg/kg/cycle. The complete response (CR) rates to both regimens were identical: 68% and 71%, respectively. In addition, there was no significant difference in disease-free and overall survival. There was a significant decrease in the incidence of WBC nadirs below 1,000/microL: 29% and 13%, respectively (P = .01). Of the non-hematologic toxicities, there was a significant reduction in the incidence of mucositis: 53% and 37%, respectively (P = .006). The major prognostic factor was tumor volume. This study confirms that vinblastine 0.3 mg/kg/cycle in PVB chemotherapy is as effective and less toxic than vinblastine 0.4 mg/kg/cycle.

Long-term follow-up of non-seminomatous testicular cancer patients with mature teratoma or carcinoma at postchemotherapy surgery

From 1979 to 1983 the EORTC GU Group treated 239 patients with disseminated non-seminomatous testicular cancer with combination chemotherapy comprising cisplatin, vinblastine and bleomycin in a prospectively controlled trial. The protocol required complete resection of residual masses after induction chemotherapy, provided that serum tumour markers were normal. 102 patients were operated on. 27 patients had mature teratoma (teratoma differentiated) in the resected specimens and 23 had viable cancer. Follow-up data were available for 26 and 22 of these patients, respectively. 23 of 26 patients (88%) with mature teratoma are alive and disease free after a follow-up of 53-110 months (median 92 months). 3 patients developed progressive disease; 1 died. A peculiar case of growing mature teratoma on the forearm is described. 13 of 22 patients (59%) with residual carcinoma are alive and disease free after a follow-up of 74-112 months (median 95 months). The prognosis of patients with carcinoma is shown to be correlated with the completeness of surgery, which in turn is correlated with the initial tumour mass before chemotherapy.

E.O.R.T.C. phase II study of cisplatin in cyvadic-resistant soft tissue sarcoma

Cis-diamminodichloroplatinum (II) (cis-DDP), 100 mg/m2 every 3 weeks was administered to 24 patients with advanced soft tissue sarcoma. All patients had received extensive prior chemotherapy and had measurable progressive disease and normal renal function on entry to the study. There were no objective responses in the 17 patients receiving an adequate trial of therapy. Nausea and vomiting were universal. Renal impairment was moderate in 2 patients and mild in 4. Serial audiometry detected hearing loss at high frequencies in 3 patients.

Surveillance of Stage 1 Non-Seminomatous Testicular Cancer — A Preliminary Report of the EORTC GU-Cooperative Group Surveillance Study

Publisher Summary This chapter presents a preliminary report of the EORTC GU-Cooperative Group Surveillance Study. The EORTC Genito-Urinary Cooperative Group decided to start a wait-and-see policy study to see if the data from the other centers could be confirmed so as to evaluate the role of lymphangiography in staging and to look for histological prognostic factors as central pathology review was possible for all patient specimens. Patients were eligible for the study if they had histologically verified nonseminomatous germ cell tumors of the testis classified according to the English classification. After they had undergone unilateral orchidectomy via an inguinal incision, the patients history and physical examination had to be negative for symptoms or signs of tumor activity. The tumor markers HCG, AFP, and LDH were to be normal at least three times after the orchidectomy, with an interval of more than 24 h between samples. Patients who had suffered a prior malignant tumor or previous treatment with cytostatic agents for nononcological reasons were ineligible. All patient data was collected at the EORTC Data Centre, Brussels, where the analyses were performed. Patients with small vessel invasion are judged high-risk and will in the future be treated in a new study protocol comparing retroperitoneal lymph node dissection with two cycles of BEP combination chemotherapy.