A phase 1 escalating single-dose and weekly fixed-dose study of cetuximab: pharmacokinetic and pharmacodynamic rationale for dosing.

Purpose: This phase 1 study evaluated the pharmacokinetic and pharmacodynamic effects of cetuximab on patients with epithelial malignancies.

Experimental Design: Following a skin and tumor biopsy, patients with advanced epithelial malignancies were randomized to receive a single dose of cetuximab at 50, 100, 250, 400, or 500 mg/m2 i.v.

A phase I trial of docetaxel and vinorelbine in patients with advanced non-small cell lung cancer.

Advanced non-small cell lung cancer (NSCLC) remains a difficult cancer to treat, and evolution of platinum-free regimens in a first-line setting is ongoing. This was a dose-finding study on the docetaxel and vinorelbine combination. Docetaxel was given at 60 mg/m(2) on day 1 only, and vinorelbine was given on days 1 and 15 starting at 20 mg/m(2), then escalated to 30 and 40 mg/m(2) in two dose cohorts.

From dogs to frogs: how pets, laboratory animals, and wildlife aided in elucidating harmful effects arising from a hazardous dumpsite.

The medical literature contains many examples of cases in which serendipitous observations have led to important findings. In the example described in this article, laboratory and field observations conducted at the Mohawk Nation Community of Akwesasne led to the important and unexpected finding that frogs once plentiful in the area were no longer observed. Laboratory tests comparing river sediments from Akwesasne to pristine sediment from Ithaca, NewYork, indicated multiple adverse health effects on developing frogs.

Phase II multicenter study of the epidermal growth factor receptor antibody cetuximab and cisplatin for recurrent and refractory squamous cell carcinoma of the head and neck.

Purpose: This multicenter phase II study was undertaken to define the efficacy and safety of cetuximab, an antiepidermal growth factor receptor chimeric human and murine monoclonal antibody, administered with cisplatin to patients with refractory metastatic or recurrent squamous cell carcinoma of the head and neck (SCCHN).

Patients And Methods: One hundred thirty-two patients were to receive two 3-week cycles with cisplatin/paclitaxel or cisplatin/fluorouracil. Patients (n = 30) with a complete or partial response continued standard therapy.

Phase I study of pegylated liposomal doxorubicin and the multidrug-resistance modulator, valspodar.

Valspodar, a P-glycoprotein modulator, affects pharmacokinetics of doxorubicin when administered in combination, resulting in doxorubicin dose reduction. In animal models, valspodar has minimal interaction with pegylated liposomal doxorubicin (PEG-LD). To determine any pharmacokinetic interaction in humans, we designed a study to determine maximum tolerated dose, dose-limiting toxicity (DLT), and pharmacokinetics of total doxorubicin, in PEG-LD and valspodar combination therapy in patients with advanced malignancies.

Phase I study of docetaxel in combination with the P-glycoprotein inhibitor, zosuquidar, in resistant malignancies.

Purpose: To determine the maximum tolerated dose, dose-limiting toxicity, and pharmacokinetics of docetaxel infused over 1 hour when given in combination with oral zosuquidar to patients with resistant solid tumors.

Experimental Design: In cycle 1, patients received docetaxel alone. In subsequent cycles, zosuquidar was administered with docetaxel, which was escalated from 75 to 100 mg/m2.

HER2 expression in salivary gland carcinomas: dependence on histological subtype.

Purpose: Previous evaluation of HER2 overexpression in salivary gland cancers indicated an incidence varying between 7 and 56%, with no clear difference among three histologically different subtypes. As part of a Phase II trial of trastuzumab for treatment of incurable salivary gland cancer, we screened 137 tumors for HER2 expression.

Experimental Design: Unstained sections of paraffin-embedded tumor samples were stained with p185/HER2 receptor antibody.

Phase I dose and sequencing study of pegylated liposomal doxorubicin and docetaxel in patients with advanced malignancies.

Background: Pegylated liposomal doxorubicin (PEG-LD) and docetaxel have single-agent activity in several malignancies. The authors conducted a Phase I trial to evaluate the maximum tolerated dose (MTD), toxicities, and effect of dose sequencing of this combination in patients with advanced malignancies.

Methods: Twenty-two patients were enrolled in this two-arm, accelerated, dose escalation trial.

Fluoxetine versus placebo in advanced cancer outpatients: a double-blinded trial of the Hoosier Oncology Group.

Purpose: To determine whether fluoxetine improves overall quality of life (QOL) in advanced cancer patients with symptoms of depression revealed by a simple survey.

Patients And Methods: One hundred sixty-three patients with an advanced solid tumor and expected survival between 3 and 24 months were randomly assigned in a double-blinded fashion to receive either fluoxetine (20 mg daily) or placebo for 12 weeks. Patients were screened for at least minimal depressive symptoms and assessed every 3 to 6 weeks for QOL and depression.

Phase I study of rubitecan and gemcitabine in patients with advanced malignancies.

Background: Rubitecan (9-nitrocamptothecin, 9-NC, Orathecin) and gemcitabine have single-agent activity in pancreatic and ovarian carcinoma. We conducted a phase I trial to evaluate the maximum tolerated dose (MTD) and toxicities of this combination in advanced malignancies.

Patients And Methods: Twenty-one patients with refractory or recurrent malignancies were enrolled in this dose escalation trial.

Phase I study of pegylated liposomal doxorubicin and gemcitabine in patients with advanced malignancies.

Background: Pegylated liposomal doxorubicin (PEG-LD) and gemcitabine have single-agent activity in breast and ovarian carcinoma patients. We conducted a Phase I trial to evaluate the maximum tolerated dose (MTD) and toxicities of this combination in patients with advanced malignancies.

Methods: Twenty-six patients with refractory or recurrent malignancies were enrolled in this dose escalation trial.

Holistic risk-based environmental decision making: a Native perspective.

Native American Nations have become increasingly concerned about the impacts of toxic substances. Although risk assessment and risk management processes have been used by government agencies to help estimate and manage risks associated with exposure to toxicants, these tools have many inadequacies and as a result have not served Native people well. In addition, resources have not always been adequate to address the concerns of Native Nations, and involvement of Native decision makers on a government-to-government basis in discussions regarding risk has only recently become common.

Phase II evaluation of amifostine as an esophageal mucosal protectant in the treatment of limited-stage small cell lung cancer with chemotherapy and twice-daily radiation.

For limited-stage small cell lung cancer, twice-daily radiation with concurrent chemotherapy improves survival rate, but has dose-limiting esophageal toxicity. The authors studied 34 patients treated with amifostine in an attempt to decrease the incidence and grade of esophagitis. The results indicate that there was no reduction in toxicity, but the authors were able to maintain the high complete response rate that had been reported previously.

Esthesioneuroblastoma: the impact of treatment modality.

Background: We evaluated the impact of treatment modality on esthesioneuroblastoma.

Methods: Between 1976 and 1996, 25 patients with esthesioneuroblastoma were treated at Mallinckrodt Institute of Radiology. There were 11 male and 14 female patients; their ages ranged from 16 to 73 years (median, 57 years).

A phase II trial of paclitaxel and cisplatin in patients with advanced carcinoma of the esophagus.

Purpose: In a phase II trial of paclitaxel, cisplatin, and fluorouracil in metastatic esophageal cancer, we identified significant activity for the combination of agents, but there was severe associated toxicity. We therefore undertook a phase II trial of paclitaxel and cisplatin without fluorouracil.

Patients And Methods: Thirty-eight patients with carcinoma of the esophagus or gastroesophageal junction were treated.

Ifosfamide in the treatment of advanced or recurrent squamous cell carcinoma of the head and neck: a phase II Hoosier Oncology Group trial.

The Hoosier Oncology Group conducted a trial evaluating ifosfamide in patients who had recurrent or metastatic squamous cell carcinoma of the head and neck. Patients must have received no prior chemotherapy for metastatic disease. If prior adjuvant chemotherapy was given, the last cycle must have been at least six months from time of recurrence.

A phase II trial of paclitaxel and cisplatin in patients with locally advanced metastatic esophageal cancer: a preliminary report.

We demonstrated in an earlier trial that paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has substantial antineoplastic activity, with acceptable toxicity, in patients with advanced metastatic esophageal cancer. Preclinical and clinical data from studies in other tumors indicate substantial additive or even synergistic activity for paclitaxel/cisplatin combination chemotherapy. We encountered substantial toxicity with a cisplatin/paclitaxel/5-fluorouracil combination.