Targeting anti-apoptotic Bcl-2 by AT-101 to increase radiation efficacy: data from in vitro and clinical pharmacokinetic studies in head and neck cancer.

Background: Pro-survival Bcl-2 family members can promote cancer development and contribute to treatment resistance. Head and neck squamous cell carcinoma (HNSCC) is frequently characterized by overexpression of anti-apoptotic Bcl-2 family members. Increased levels of these anti-apoptotic proteins have been associated with radio- and chemoresistance and poor clinical outcome.

Postoperative chemoradiotherapy in gastric cancer--a phase I-II study of radiotherapy with dose escalation of weekly cisplatin and daily capecitabine chemotherapy.

Background: Postoperative chemoradiotherapy with concurrent 5-fluorouracil improves gastric cancer outcome. We previously demonstrated that chemoradiotherapy with a more intensified--and therefore potentially more effective--schedule with daily cisplatin and oral capecitabine is feasible. Because such an intensive schedule requires an extensive logistic infrastructure which is not available in every hospital, we additionally investigated the tolerability of this combined regimen with weekly instead of daily cisplatin in a dose-escalation study.

Postoperative chemoradiotherapy in gastric cancer -- a Phase I/II dose-finding study of radiotherapy with dose escalation of cisplatin and capecitabine chemotherapy.

We hypothesised that gastric cancer outcome could be improved with more effective and intensified postoperative chemoradiotherapy. This phase I/II study was performed to determine the maximal tolerated dose (MTD) and toxicity profile of postoperative radiotherapy with concurrent daily cisplatin and capecitabine. Patients were treated with capecitabine 1000 mg m(-2) twice a day (b.

A phase I-II study of postoperative capecitabine-based chemoradiotherapy in gastric cancer.

Background: The Intergroup 0116 randomized study showed that postoperative 5-fluorouracil-based chemoradiotherapy improved locoregional control and overall survival in patients with gastric cancer. We hypothesized that these results could be improved further by using a more effective, intensified, and convenient chemotherapy schedule. Therefore, this Phase I-II dose-escalation study was performed to determine the maximal tolerated dose and toxicity profile of postoperative radiotherapy combined with concurrent capecitabine.

Prospective study on late renal toxicity following postoperative chemoradiotherapy in gastric cancer.

Purpose: Postoperative chemoradiotherapy in gastric cancer improves locoregional control and survival. Reports on late toxicity, however, have been scarce thus far. Because renal toxicity is one of the most serious late complications in upper abdominal radiotherapy, we prospectively analyzed kidney function in patients who underwent postoperative chemoradiotherapy for gastric cancer.

Phase I and pharmacokinetic study of combined treatment with perifosine and radiation in patients with advanced solid tumours.

Purpose: Perifosine is an orally applicable, membrane-targeted alkylphosphocholine analogue with antitumour activity and radiosensitising properties in preclinical models. The purpose of this phase I study was to determine the feasibility and tolerability of concurrent daily perifosine and radiation in patients with advanced cancer.

Patients And Methods: Starting dose of perifosine was 50 mg/day; dose escalation was in steps of 50mg.

Phase I and pharmacological study of daily oral administration of perifosine (D-21266) in patients with advanced solid tumours.

Alkylphosphocholines are a novel class of antitumour agents structurally related to ether lipids that interact with the cell membrane and influence intracellular growth signal transduction pathways. We performed a phase I trial with an analogue of miltefosine, perifosine (D-21266), which was expected to induce less gastrointestinal toxicity. Objectives of the trial were: to determine the maximum-tolerated dose (MTD) for daily administration, to identify the dose-limiting toxicity (DLT) of this schedule, to assess drug accumulation and to determine the relevant pharmacokinetic parameters.

Urinary and fecal excretion of topotecan in patients with malignant solid tumours.

Purpose: The objectives of the study were to determine the pharmacokinetics and routes of excretion of topotecan following intravenous or oral administration to patients with refractory solid tumours.

Methods: Patients were randomized to receive either oral (2.3 mg/m(2)) or intravenous (1.

Feasibility and pharmacokinetics of intraperitoneal suramin in advanced malignancy.

Purpose: Bioactive lipids have been causally linked to intraabdominal malignancies such as ovarian cancer. In advanced tumors confined to the peritoneal cavity. inhibition of lipid growth factors present in ascites might induce tumor remissions.

Phase I and pharmacologic study of weekly doxorubicin and 1 h infusional paclitaxel in patients with advanced breast cancer.

Doxorubicin and paclitaxel both display strong antitumor activity in the treatment of breast cancer. The optimal schedule of this combination, however, remains undefined. In this phase I and pharmacologic study, we administered weekly 12 mg/m2 doxorubicin as a bolus infusion immediately followed by a 1 h 80 mg/m2 paclitaxel infusion to patients with metastatic breast cancer.

Pharmacologic study of 3-hour 135 mg M-2 paclitaxel in platinum pretreated patients with advanced ovarian cancer.

Paclitaxel (Taxol(R)) is an active agent in platinum-refractory ovarian cancer. Since the available pharmacokinetic data of 135 mg m-2 paclitaxel administered by 3-h infusion are scarce and fragmented, we now describe a comprehensive pharmacologic study in a group of 13 patients who were pretreated with platinum for advanced ovarian cancer. The mean paclitaxel AUC was 10.

Docetaxel alternating with epirubicin and cyclophosphamide: a feasibility study in breast cancer patients.

Docetaxel is one of the most active drugs used in the treatment of breast cancer. However, its major side-effect, myelosuppression, hampers full-dose combination chemotherapy. We have, therefore, developed an alternating schedule of docetaxel with epirubicin and cyclophosphamide, together with granulocyte colony-stimulating factor, to ameliorate neutropenia.

Carboplatin and paclitaxel in patients with advanced ovarian cancer: a dose-finding study.

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) combined with cisplatin seems the new standard of care for ovarian cancer patients. Since carboplatin lacks the neurotoxicity of cisplatin with an equal antitumor activity against ovarian cancer, it was chosen as the next logical step for combination chemotherapy with paclitaxel. In 46 patients an alternating dose-escalation trial has been performed.

Telephone-based nursing intervention improves the effectiveness of the informed consent process in cancer clinical trials.

Purpose: Here we report the results of a randomized study undertaken to test the efficacy of a supplementary, telephone-based nursing intervention in increasing patients' awareness and understanding of the clinical trials in which they are asked to participate.

Methods: During a 12-month period, 180 cancer patients who were approached to participate in a phase II or III clinical trial were randomized to undergo either of the following: (1) standard informed consent procedures based on verbal explanations from the treating physician plus written information (controls); or (2) standard informed consent procedures plus a supplementary, telephone-based contact with an oncology nurse (intervention). For purposes of evaluation, face-to-face interviews were conducted with all patients approximately 1 week after the informed consent process had been completed.

Treatment of patients with IVCS and gross oedema and ascites with diuretic combination and ACE-inhibitors: relation to baseline PRA and PAC.

Objective: (1) To assess plasma renin activity (PRA) and plasma aldosterone concentration (PAC) in patients with inferior vena cava syndrome (IVCS). (2) To study in an open fashion the efficacy of loop diuretic treatment, single, or in combination with an ACE-inhibitor or with spironolactone.

Methods: In 13 patients PRA and PAC were measured and related to urinary sodium excretion (UNa).

Phase I/II study of intraperitoneal mitoxantrone in refractory ovarian cancer.

Background: Mitoxantrone has demonstrable clinical activity when administered intravenously in a wide range of malignancies. The feasibility and toxicity of intra-peritoneal administration was established in a phase I study. The optimal dose from the phase I was subsequently evaluated in a phase II study.

Etoposide, leucovorin, 5-fluorouracil (ELF) combination chemotherapy for advanced gastric cancer: experience with two treatment schedules incorporating intravenous or oral etoposide.

Background: Because the ELF regimen (etoposide, leucovorin and 5-FU) in advanced gastric cancer was recently advocated as an active, non-toxic schedule, and drug scheduling of etoposide proved to be important, we performed a pilot study using the original ELF regimen (A), followed by a phase II study of a modified ELF schedule (B) using oral etoposide.

Patients And Methods: Of the 40 patients entered in the consecutive trials 15 were treated according to the original ELF (A) and 25 according to the modified ELF regimen (B). The primary tumor was originally in the stomach in 22 and the oesophago-cardiac junction in 18.

Effects of interleukin-3 on myelosuppression induced by chemotherapy for ovarian cancer and small cell undifferentiated tumours.

Two clinical studies were undertaken to study the toxicity profile and effects of interleukin-3 (rhIL-3) on chemotherapy-induced myelosuppression. Fifteen patients with recurrent ovarian carcinoma were treated with high dose carboplatin (800 mg m-2). All patients received 5.

Age-dependent vitamin D status and vertebral condition of white women living in Curaçao (The Netherlands Antilles) as compared with their counterparts in The Netherlands.

Plasma vitamin D metabolites and parathyroid hormone concentrations of two groups of white women, aged 26-46 and 63-83 y, in Curaçao were studied to evaluate the effect of yearlong abundant sunlight on frequency of vertebral compression fractures in elderly women. 25-Hydroxyvitamin D of the younger group (median, 116 nmol/L) was higher than that of the older group (75 nmol/L). Both groups had higher 25-hydroxyvitamin D compared with approximately age-matched counterparts in The Netherlands during autumn and winter (50 and 25 nmol/L, respectively).

Central venous catheter associated thrombosis of major veins: thrombolytic treatment with recombinant tissue plasminogen activator.

Objective: Major thromboses can occur in the venous system in association with central venous catheters. This usually necessitates removal of the catheter.

Methods: The effectiveness of low dose recombinant tissue type plasminogen activator (rt-PA) in combination with heparin was assessed in patients with central venous catheter associated thrombosis.

Feasibility study of high-dose carboplatin and etoposide in the salvage treatment of testicular cancer.

Eleven patients with testicular cancer, either relapsing after or refractory to cisplatin-based chemotherapy, underwent salvage chemotherapy with high-dose carboplatin (800 mg/m2 on day 1) and high-dose etoposide (500 mg/m2 on days 1, 3 and 5). A total of 21 courses were administered. The major toxicity consisted of profound myelosuppression.

Replacement of cisplatin with carboplatin in combination chemotherapy against ovarian cancer: long-term treatment results of a study of the Gynaecological Cancer Cooperative Group of the EORTC and experience at The Netherlands Cancer Institute.

Carboplatin-based chemotherapy has been evaluated in three studies of ovarian cancer patients. In the first, combination cisplatin and carboplatin plus doxorubicin/hexamethylmelamine/cyclophosphamide were compared as first-line treatment of ovarian cancer in 341 women with stage IIB to IV disease. There were no observed differences in results between the two treatment groups.

Clinical pharmacokinetics of mitoxantrone after intraperitoneal administration.

The pharmacokinetics of intraperitoneally (i.p.) injected mitoxantrone was determined in plasma and peritoneal dialysate taken from five patients presenting with cancer confined to the peritoneal cavity over a sampling period of 1 week.