Phase II trial of 7-day continuous 5-fluorouracil infusion in the treatment of advanced colorectal carcinoma.

Thirty-eight patients with advanced colorectal adenocarcinoma were entered on a phase II trial of 5-fluorouracil (5-FU) in continuous infusion, using a portable pump. Half of the patients had been pretreated (n = 19) and 16 of them had received intravenous bolus 5-FU alone or in combination. At the first cycle patients received continuous intravenous 5-FU at the dose of 650 mg/m2 per day for 7 consecutive days. Doses were escalated during the following cycles and adjusted according to the toxicities encountered in the previous cycle. Treatment was repeated every 3 weeks. A mean dose of 750 mg/m2/day (500-1,000) was administered for a mean number of 10 (1-25) cycles. We observed 1 complete response, 7 partial responses for a response rate of 21 +/- 13% (CI95%), 16 had stable disease (42%) and 14 a progression (37%). In 2 patients subsequently the residual tumors could be excised after chemotherapy. Median survival was 13.5 months. Toxicity was: grade 2 leukopenia in 1 patient (3%), mucositis grade 2-4 in 11 patients (29%), diarrhea grade 2-3 in 7 patients (18%), and hand and foot syndrome in 12 patients (31%). There was a correlation between the mean dose administered and the responses. However no clear correlation was found between toxicity and tumoral response for the first two cycles. These results confirm the limited efficacy of continuous intravenous 5-FU and its good tolerance in ambulatory patients.

Long-term survivors after salvage high dose chemotherapy with bone marrow rescue in refractory germ cell cancer.

Between April 1984 and May 1985, 17 heavily pretreated patients with relapsing or refractory germ cell tumours were treated with cisplatin 40 mg/m2/day, days 1-5; etoposide 350 mg/m2/day, days 1-5; cyclophosphamide 1600 mg/m2/day, days 2-5 and autologous bone marrow transplantation on day 8 as consolidation of conventional salvage chemotherapy. None of the 11 refractory patients and 4 of the 6 responders to prior salvage treatment are long-term survivors at 68, 72, 74 and 74 months. Mean aplasia duration was 17 days and there were 7 documented episodes of septicaemia in 17 febrile patients. 1 patient died of treatment. Among the 4 survivors, 2 patients have a sustained grade II invalidating neuropathy. We conclude that this regimen is not recommended as salvage therapy in refractory patients but may be a useful consolidation treatment in patients responding to conventional salvage chemotherapy.

[Chemotherapy in advanced transitional cell carcinoma of the urinary tract. Phase II trial of a combination of doxorubicin and cisplatin]. / Chimiothérapie des stades avancés de carcinomes à cellules transitionnelles des voies urinaires. Essai phase II d'une association de doxorubicine et de cisplatine.

Between January 1, 1983 and December 31, 1984, 18 patients with advanced transitional cell carcinoma of the urothelium were treated in a Phase II trial with doxorubicin 45 mg/sqm plus cisplatin 90/mg/sqm/day every four weeks. 17 patients were evaluable for response. There were: 4 partial responses (24% of response objective effects, 95% confidence limits are 15% and 33%) and 13 failures. The median survival was 18.5 months for responders and 10 months for non responders.

Sarcoidosis and testicular germ cell tumor. Case report.

The authors describe the case of a patient with stage II non seminomatous germinal cell tumor of the testis with a generalized sarcoidosis. They review the existing literature and discuss the problem of diagnosis.

Treatment of high-risk gestational trophoblastic disease with chemotherapy combinations containing cisplatin and etoposide.

The authors have treated 22 patients with high-risk gestational trophoblastic disease (GTD) by cisplatin-etoposide-containing combinations. Sixteen patients were treated with dactinomycin, platinum, and etoposide combination (APE regimen) and six patients had platinum and etoposide combination (PE regimen). Fourteen patients were treated for resistant or relapsing GTD after first-line therapy, and eight patients initially. All 22 patients were high risk according to the World Health Organization prognostic score values. Sustained complete remission was achieved in 19 patients (86%). All eight patients who received treatment as initial therapy were cured (100%) whereas only 11 patients were cured among the 14 patients who failed prior chemotherapy (78%). Hematologic and renal toxicities were limited and no treatment-related deaths occurred in this group of patients. Cisplatin and etoposide could be more widely used in chemotherapeutic combinations for high-risk gestational trophoblastic disease.

Phase II trial of combination chemotherapy with fluorouracil (F), doxorubicin (A), and cisplatin (P) (Fap) in hormonally resistant metastatic prostatic adenocarcinoma.

From October 1985 to December 1986, 25 patients with advanced prostatic carcinoma were entered in a phase II trial and were administered fluorouracil (F) 600 mg/m2, on days 1 and 2, doxorubicin (A) 40 mg/m2, on day 1, and cisplatin (P) 90 mg/m2, on day 1, every month. The response was evaluated after three cycles of chemotherapy according to National Prostatic Cancer Project criteria. There were no complete remission, 1 partial remission, 13 stabilizations, 11 progressions. Toxicity was assessed using WHO criteria. Alopecia and vomiting were universal; there were 11 grade 1 anemias, 2 aplasias, and 1 grade 1 renal toxicity. A FAP regimen appears to exert a marginal effect in advanced prostatic carcinoma.

Prognostic factors in advanced nonseminomatous testicular cancer. A multivariate logistic regression analysis.

In order to define prognostic factors for advanced stage of nonseminomatous germ cell tumors (NSGCT) of the testis, the authors reviewed 84 patients treated from 1978 through 1985. The survival rate was 51% at 3 years. Patients with elevated seric levels of human chorionic gonadotropin (HCG) and/or alpha-fetoprotein (AFP), or the presence of an abdominal mass had significantly worse survival. Only HCG and AFP levels retained their significance when multivariate Cox analysis was performed. The probability that a patient achieves a complete remission (CR) was assessed by a function of certain patient characteristics using a multivariate logistic regression analysis. The significant variables were a function of HCG and AFP values. Since both variables are related to the CR rate and survival the authors define the obtention of a CR as a unique outcome of interest. The probability of a CR greater than 70% adequately separates the patients into two prognostic subgroups. This model currently is being used to enrole NSGCT patients in a prospective modulated clinical trial according to these prognostic factors.

Twelve-year experience with chemotherapy in adult metastatic renal cell carcinoma at the Institut Gustave-Roussy.

One hundred fifty-three adult patients with metastatic renal carcinoma were treated over a 12-year period. Five successive chemotherapeutic protocols were used: vincristine or teniposide plus CCNU, elliptinium weekly or monthly, ifosfamide, and lastly, a multidrug regimen with adriamycin, vindesine, cyclophosphamide, cisplatinum, and dacarbazine. Results obtained with these different consecutive protocols were very disappointing with only ten (7%) objective responses encountered.

Phase II trial with high-dose elliptinium acetate in metastatic renal cell carcinoma.

Sixteen patients with adult metastatic renal cell carcinoma were treated with elliptinium acetate, 80 mg/m2.day, for 3 consecutive days every 3 weeks. Among the 14 patients evaluable, no objective effects were observed. The toxicity was mild and no patients experienced intravascular hemolysis.

[Isolated hepatic metastases. Treatment by intra-arterial chemotherapy using a subcutaneous access chamber]. / Métastases hépatiques isolées. Traitement par chimiothérapie intra-artérielle par l'intermédiaire d'une chambre d'accès sous-cutanée.

Twenty eight patients with isolated liver metastases of colorectal origin have been treated with discontinuous intra-arterial chemotherapy. This treatment was performed weekly with a surgically implanted subcutaneous access chamber. In all the patients the metastases were non-resectable and involved less than 75% of the liver. The first six patients were investigated in a phase I study which demonstrated that the method was well tolerated and provided a normal life at a lower price than the totally implanted pump. A subsequent phase II study included 22 patients. After implantation, they received an 8-hour infusion of 5 Fu 1 g/m2 each day for 8 consecutive days and after discharge, a weekly 8-hour infusion of 5 Fu 1 g/m2 and mitomycin C 1.5 mg/m2 as out-patients. Twenty-one patients have now been followed up for more than 3 months and are assessable in terms of response: we observed 4/21 complete responses, 6/21 partial responses, 3/21 minor responses, 7/21 stable disease and 1/21 progression. The objective response rate was 48%. The complication rate was low (2 leukopenias and 2 duodenal ulcerations) and comfort excellent with normal life between courses. In conclusion, with discontinuous intra-arterial chemotherapy we obtained the same response rate as with the totally implanted pump, with good tolerance and quality of life and perhaps a lower rate of complication. The two methods should now be compared in a randomized trial.

[Intermittent and ambulatory intra-arterial chemotherapy using a subcutaneous access chamber in the treatment of isolated hepatic metastases. Preliminary results]. / Chimiothérapie intra-artérielle discontinue et ambulatoire par l'intermédiaire d'une chambre d'accès sous-cutanée dans le traitement des métastases hépatiques isolées. Résultats préliminaires.

Discontinuous daily ambulatory intra-arterial chemotherapy using a needle access chamber implanted subcutaneously was achieved for treatment of nonresectable isolated hepatic metastases. This original approach is a compromise between the uncomfortable exterior catheter and the exorbitant cost of a pump implant. Phase I study (6 cases) brought out the technical problems involved in this method. Phase II study (presently 11 cases) of only primary colonic or rectal tumor metastases treated with 5-fluorouracil and mitomycin C was undertaken. The preliminary results of this small series yields 64 percent objective improvement for which 55 percent are complete remissions.

[Treatment of hepatic metastases with unknown primary cancer]. / Traitement des métastases hépatiques sans cancer primitif connu.

A series of 15 cases of hepatic metastases of unknown etiology is reported. All patients had a needle biopsy of the liver. The search for primary tumor was restricted to only those tumors requiring specific therapeutic protocols. Patients received intravenous chemotherapy in accordance with histopathological classification. This chemotherapy induced objective improvement in 46 percent of cases. The average survival of responding patients is about 16 months. Three patients had complete remissions and underwent a second laparotomy with excision of necrotic lesions in one case and installation of a catheter for endarterial hepatic chemotherapy in another. The investigators propose a diagnostic and therapeutic protocol for such patients.

[Hematologic manifestations of cancers of the prostate]. / Manifestations hématologiques des cancers de la prostate.

Authors study six cases of prostatic adenocarcinoma with bone marrow metastatic involvement. Hematological manifestations can be: intravascular coagulation with anemia and myelemia. The heparin permits to control the intravascular coagulation when waiting the effect of hormonotherapy, chemotherapy or radiotherapy.

[Relapses of malignant nonseminomatous germinal testicular tumors]. / Les rechutes des tumeurs malignes germinales non séminomateuses du testicule.

18 relapses of non seminomatous germ cell cancer of the testis are studied, among a group of 112 patients treated from 1974 to 1978, of which 90 are in complete remission. The study of these cases shows the bad prognosis value of yolk sac tumor component at histological examination. Relapses are more frequent in the stages with lymph node involvement treated by retroperitoneal lymphadenectomy followed by chemotherapy without cis-platinum. Cis-platinum chemotherapy decreases relapse rate in theses stages and increases complete remission rate in metastatic stages.