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Biomedical subjects

J A Wils

Publications and source records attributed to J A Wils.

At least 37 records · Page 2Linked to original sources
PubMed1994

Phase II trial for intraperitoneal cisplatin plus intravenous sodium thiosulphate in advanced ovarian carcinoma patients with minimal residual disease after cisplatin-based chemotherapy--a phase II study of the EORTC Gynaecological Cancer Cooperative Group.

On the basis of its efficacy against ovarian carcinoma and its safe peritoneal administration, cisplatin administered by the intraperitoneal route was studied in a phase II multicentric trial. 34 patients with good performance status and residual disease less than 1 cm were treated with a 90 mg/m2 dose (60 mg/m2 at first cycle), administered in the abdominal cavity every 3 weeks for at least four cycles. In case of haematological or renal toxicity, intravenous sodium thiosulphate was perfused simultaneously with intraperitoneal cisplatin with protective intent. 25 patients were evaluable for response: 3 patients had pathological complete response and 1 patient had a microscopic disease (16% response rate in evaluable patients). Systemic toxicity was mild, and sodium thiosulphate clearly protected against leucopenia (6 patients) and renal toxicity (8 patients). Local side-effects were evaluable in 34 patients with 2 cases of infectious peritonitis, 1 of wound infection and 2 of haemorrhage. Of the 147 evaluable chemotherapy cycles, nine resulted in partial and one in total inflow obstruction, for which 4 patients needed surgical procedures for catheter-related complications, and 1 patient died of acute abdominal complications after such a procedure. We conclude that 90 mg/m2 intraperitoneal cisplatin has activity in pretreated patients with minimal residual disease, and that thiosulphate protects against haematological and renal toxicities. Only a randomised study can demonstrate a true benefit, which will have to be balanced with the toxicity of intraperitoneal drug administration.

Aged↗
PubMed1994

Multimodality treatment of locally advanced pancreatic cancer.

BACKGROUND: The prognosis of locally advanced pancreatic cancer is poor (median survival 3-5 months). In view of the localized character of this disease several groups have explored the value of combined modality treatment. The conditions are that a good local treatment and an effective systemic treatment are available. PATIENTS AND METHODS: The results of irradiation and of chemotherapy in advanced disease are reviewed. RESULTS: An overview of combined modality treatment has been given. CONCLUSIONS: Results of combined modality treatment are superior to irradiation alone or to symptomatic treatment.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Gastric epithelial atypia complicating hepatic arterial infusion chemotherapy.

Severe gastric lesions developed in five patients during hepatic arterial infusion chemotherapy employing 5-fluorouracil plus either leucovorin or mitomycin C. Ulceration with marked epithelial atypia was observed with striking structural distortion and cellular pleomorphism of the affected gastric mucosa. These features should be considered to be a complication of such treatment and should not be misinterpreted as malignancy.

Aged↗
PubMed1993

Mitoxantrone, leucovorin and high-dose infusional 5-fluorouracil: an effective and well-tolerated regimen for the treatment of advanced breast cancer.

Mitoxantrone and 5-fluorouracil (5-FU) are active drugs with a favourable toxicity profile in advanced breast cancer. The activity of 5-FU can be enhanced by modulation with leucovorin. Continuous infusion of 5-FU yields a superior activity with less toxicity compared with bolus injections. 27 patients with advanced breast cancer, 22 of them pretreated, received intravenous (iv) mitoxantrone, 14 mg/m2, day 1, iv leucovorin, 300 mg, days 1 and 15, and 5-FU, 4 g, 48-h infusion, days 1 and 2, 15 and 16, once every 28 days (MLF regimen). Leucovorin was administered either as a bolus prior to the 5-FU infusion or mixed together with the 5-FU during the first 24 h. There were 12 partial responses, 9 patients had stable disease, and 5 had progressive disease. 1 patient was not evaluable because of concomitant irradiation of the target lesion. The overall response rate was 46%; for previously untreated patients it was 100% and for pretreated patients it was 33%. Grade 3 nausea/vomiting was noted in 7 evaluable patients (26%) and grade 4 haematological toxicity in 1 patient (4%). Only 1 patient had complete alopecia. The median duration of response was 13 months in untreated, and 12 months in pretreated patients. It was concluded that MLF is an active regimen in advanced breast cancer, even in highly pretreated patients, with moderate and manageable toxicity. Assessment in first-line treatment appears to be of interest.

Adult↗
PubMed1993

Activity of cisplatin in adenocarcinoma of the pancreas.

The activity of cisplatin in metastatic adenocarcinoma of the pancreas was assessed in 33 patients. Cisplatin was administered in a dose of 100 mg/m2, every 4 weeks. There were 2 complete responses and 5 partial responses (a response rate of 21%). The median duration of response was 5 months (range, 2+ to 15 months). Cisplatin is a modestly active drug in advanced pancreatic cancer.

Adenocarcinoma↗
PubMed1992

Chemotherapy for gastrointestinal cancer: new hopes or new disappointments?

Since the end of the eighties relevant progress has been made in the treatment of gastrointestinal tract cancer, as well in advanced disease as in the adjuvant setting. The neoadjuvant treatment of localized esophageal and gastric cancer is of high interest, and especially the adjuvant treatment of colorectal cancer provides a realistic hope for further progress in the years not too far ahead. Results of recent studies with implications for future trials are discussed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

High-dose fluorouracil: a new perspective in the treatment of colorectal cancer?

It is possible that there exists a relationship between the dose intensity of fluorouracil (5-FU) and the response in colorectal cancer. Because a very high dose intensity can be achieved with weekly 24 to 48 hours continuous infusions of 5-FU, this treatment schedule appears attractive. A review of available data suggest that with continuous infusions an enhanced treatment outcome as opposed to treatment with standard bolus injections can be achieved. The superiority of "modulated" standard dose 5-FU versus the maximum tolerated dose of weekly continuous infusion of 5-FU alone, should be investigated. Future studies should reveal whether a superior treatment outcome can be achieved by modulation of high-dose 5-FU.

Clinical Trials as Topic↗
PubMed1991

Chemotherapy in pancreatic cancer: a rational pursuit?

A review on the chemotherapy in advanced pancreatic cancer is presented. Pancreatic cancer is an extremely chemotherapy resistant tumor and results of cytostatic drug treatment so far are unsatisfactory. For patients with locally advanced disease the combination of chemo- and radiotherapy may palliate some patients. To date no standard treatment is available and patients should be entered in clinical protocols assessing new treatment options.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Perspectives in chemotherapy of advanced gastric cancer.

A review of recent phase II and III studies in advanced gastric carcinoma is presented. Several combination regimens have been developed with high activity in locally advanced and metastatic disease. Among them are etoposide plus adriamycin plus cisplatin (EAP), etoposide plus 5-fluorouracil plus leucovorin (ELF), continuous infusion 5-fluorouracil plus cisplatin and high dose methotrexate plus 5-fluorouracil plus adriamycin (FAMTX). In locally advanced disease a resectability rate of +/- 50% has been reported with these protocols. So far only FAMTX has demonstrated superiority compared with 5-fluorouracil, adriamycin and mitomycin (FAM), which regimen has been considered 'standard' treatment for many years. Randomized studies in which the other regimens are being more definitely assessed are underway.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Sequential high-dose methotrexate and fluorouracil combined with doxorubicin--a step ahead in the treatment of advanced gastric cancer: a trial of the European Organization for Research and Treatment of Cancer Gastrointestinal Tract Cooperative Group.

In a prospective phase III multicenter trial, 213 patients with advanced measurable or nonmeasurable gastric cancer were randomized to receive methotrexate (MTX), fluorouracil (5-FU), and Adriamycin (doxorubicin; Farmitalia Carlo Erba, Milan, Italy) (FAMTX) or 5-FU, Adriamycin, and mitomycin (FAM). The results show a significantly superior response rate (41% v 9% [P less than .0001]), and survival (median, 42 weeks v 29 weeks [P = .004]) for FAMTX. There was a cumulative thrombocytopenia in FAM and not in FAMTX. The FAMTX protocol should be the reference treatment in future clinical trials that seek to improve the therapeutic outcome in advanced gastric cancer.

Adult↗
PubMed1990

Long-term follow-up of patients with advanced ovarian carcinoma treated with debulking surgery and chemotherapy consisting of cisplatin, doxorubicin, and cyclophosphamide. Gynecologic Oncology Group of the Comprehensive Cancer Center.

Between June 1980 and December 1984, 88 patients with stage III-IV ovarian carcinoma were entered in a study evaluating the role of debulking surgery and chemotherapy consisting of cyclophosphamide, doxorubicin, and cisplatin intravenously on day 1, every 4 weeks (CAP-1). The results after a median follow-up of 62 months (range 41-93 months) are presented. The median survival of all patients was 24 months (30 alive, 58 dead). The 5-year progression-free survival of all patients was 27% and the overall survival was 33%. Of patients with stage III disease debulked to lesions less than or equal to 1.5 cm before the initiation of chemotherapy (n = 34) the 5-year progression-free survival was 52%. Of 31 patients with a histologically documented complete response the median survival was 55+ months; 9 (29%) of them relapsed as opposed to 8 of 10 achieving microscopic residual disease at second look. Of 22 patients with stage IV disease, 20 died. This report confirms that patients who have undergone surgical removal of of bulk tumor and who achieve a complete remission have an improved survival outcome.

Altretamine↗
PubMed1988

Myeloprotective effect of high dose medroxyprogesterone acetate (MPA).

Results of clinical studies in advanced and, recently, also in early breast cancer have shown a clear protective effect of high dose medroxyprogesterone acetate (MPA) on the bone marrow toxicity induced by chemotherapy. The underlying mechanism of this phenomenon is unsettled and in vitro studies have yielded contradictory results. The results of these clinical and in vitro studies are summarized. The myeloprotective effect may have important therapeutical implications.

Antineoplastic Combined Chemotherapy Protocols↗