Werner Scheithauer

Clinical trials of agents that reverse multidrug resistance. A literature review

Background. The discovery of the P‐170 glycoprotein as a mediator of multidrug resistance (MDR) represents one of the most important research accomplishments in antineoplastic pharmacology during the last decade. Demonstration of P‐170 in epithelial tissues, untreated and chemotherapeutically pretreated human malignancies, and identification of various agents capable of reversing resistance in vitro generated enthusiasm for clinical studies throughout the world. The authors provide an overview of the current status of clinical investigations of MDR1 reversing agents in hematologic and solid malignancies.

A phase II trial of biweekly high dose gemcitabine for patients with metastatic pancreatic adenocarcinoma

Although the novel cytidine analog gemcitabine has shown superior antitumor activity compared with weekly bolus 5‐fluorouracil in patients with advanced pancreatic carcinoma, further improvements of therapeutic results are warranted. The current Phase II study was initiated to investigate whether this might be achieved by dose intensification.

Chemotherapy for the treatment of patients with primary high grade gastric B-cell lymphoma of modified Ann Arbor Stages IE and IIE.

Surgical intervention and combined modality treatment including radiation and chemotherapy have been studied widely in patients with high grade gastric B‐cell lymphoma, whereas to the authors knowledge the role of chemotherapy alone in patients with localized disease has not been investigated extensively.

Oxaliplatin plus raltitrexed in patients with advanced colorectal carcinoma

Oxaliplatin and raltitrexed both are active anticancer agents in the treatment of patients with advanced colorectal carcinoma: They have different mechanisms of action and toxicity profiles and have shown at least additive effects in experimental and preliminary clinical studies. The aim of this disease oriented Phase I–II study was to determine the maximum tolerated dose (MTD), the dose‐limiting toxicities (DLT), and the objective response rate of this combination in patients with advanced colorectal carcinoma.

A phase II trial of 5-fluorouracil, leucovorin, and recombinant alpha-2b-interferon in advanced adenocarcinoma of the pancreas

Background. Preclinical and clinical data suggest that both leucovorin (LV) and interferon (IFN) can augment the cytotoxic effects of 5‐fluorouracil (5‐FU). Based on the rationale of biochemical double modulation, the current Phase I1 study was undertaken.

Treatment of patients with advanced nonsmall cell lung carcinoma using docetaxel and gemcitabine plus granulocyte-colony stimulating factor

A combination regimen comprised of docetaxel, gemcitabine, and granulocyte‐colony stimulating factor (G‐CSF) was studied in patients with advanced nonsmall cell lung carcinoma (NSCLC) to determine its antitumor efficacy and tolerance.

Randomized comparison of fluorouracil and leucovorin therapy versus fluorouracil, leucovorin, and cisplatin therapy in patients with advanced colorectal cancer

Background. Because of experimental and preliminary clinical evidence that additional modulation of the biochemical pharmacology and cytotoxicity of 5‐fluorouracil (5‐FU) and leucovorin (LV) may be possible by combination of these agents with cisplatin (CDDP), the authors undertook a prospective randomized trial in patients with colorectal cancer.

Effective radiochemotherapy with cisplatin and etoposide for the management of patients with locally inoperable and metastatic esophageal carcinoma

The limited therapeutic value of available chemotherapeutic drug combinations in patients with advanced esophageal carcinoma, the documented synergistic activity of etoposide and cisplatin, which might be further enhanced by simultaneous radiotherapy, and promising though only preliminary therapeutic results with this combination regimen have stimulated the present Phase II trial. The specific aim of the study was to determine the efficacy and tolerance of this combined treatment approach in previously untreated patients with either local regional unresectable or metastatic esophageal carcinoma.

Fatal liver failure after the administration of raltitrexed for cancer chemotherapy

Acute fatal liver failure is a relatively rare event after the administration of antineoplastic drugs. To the authors knowledge, there have been no published reports of this phenomenon after the administration of the widely applied cytotoxic agent raltitrexed.

A phase I-II study of epirubicin, 5-fluorouracil, and leucovorin in advanced adenocarcinoma of the stomach.

Background. To determine the maximum tolerated dose of epirubicin for use in combination with 5‐fluorouracil (5‐FU) and low‐dose leucovorin (LV), a Phase I–II trial was conducted in 37 patients with advanced gastric carcinoma.