Correlation between development of rash and efficacy in patients treated with the epidermal growth factor receptor tyrosine kinase inhibitor erlotinib in two large phase III studies.

Purpose: Data from two large phase III studies were analyzed to characterize the correlation between the occurrence of rash during treatment with the epidermal growth factor receptor inhibitor erlotinib and improved clinical outcomes.

Experimental Design: Overall survival, progression-free survival (PFS), and tumor response were compared between patients in a rash-evaluable subset who did or did not develop rash in National Cancer Institute of Canada Clinical Trials Group Studies BR.21 (single agent in non-small-cell lung cancer, n = 444 in erlotinib group and n = 229 in placebo group) and PA.

Effects of smoking on the pharmacokinetics of erlotinib.

Purpose: To compare the pharmacokinetic variables of erlotinib in current smokers with nonsmokers after receiving a single oral 150 or 300 mg dose of erlotinib.

Experimental Design: This was a single-center, open-label pharmacokinetic study in healthy male subjects. Subjects were enrolled into two treatment cohorts based on smoking status (current smokers and nonsmokers).

Whole-brain radiotherapy with or without efaproxiral for the treatment of brain metastases: Determinants of response and its prognostic value for subsequent survival.

Purpose: To determine the prognostic factors for radiographic response and its prognostic value for subsequent survival in patients undergoing whole-brain radiotherapy (WBRT) for brain metastases.

Methods And Materials: Five hundred fifteen eligible patients were randomized in a phase III trial evaluating WBRT and supplemental oxygen with or without efaproxiral, an allosteric modifier of hemoglobin that reduces hemoglobin oxygen-binding affinity and enhances tumor oxygenation, potentially increasing tumor radiosensitivity. Brain images were obtained at baseline and at scheduled follow-up visits after WBRT.

Phase III study of efaproxiral as an adjunct to whole-brain radiation therapy for brain metastases.

Purpose: To determine whether efaproxiral, an allosteric modifier of hemoglobin, improves survival in patients with brain metastases when used as an adjunct to whole-brain radiation therapy (WBRT).

Patients And Methods: Patients with brain metastases from solid tumors and a Karnofsky performance score of > or = 70 were randomly assigned to receive WBRT with supplemental oxygen and either efaproxiral at 75 or 100 mg/kg (efaproxiral arm) or no efaproxiral (control arm). The primary end point was survival.

Phase II multicenter study of induction chemotherapy followed by concurrent efaproxiral (RSR13) and thoracic radiotherapy for patients with locally advanced non-small-cell lung cancer.

Purpose: Efaproxiral (RSR13) reduces hemoglobin oxygen-binding affinity, facilitates oxygen release, and increases tissue pO2. We conducted a phase II multicenter study that assessed the efficacy and safety of efaproxiral when administered with thoracic radiation therapy (TRT), following induction chemotherapy, for treatment of locally advanced non-small-cell lung cancer (NSCLC).

Patients And Methods: Fifty-one patients with locally advanced NSCLC were enrolled at 13 sites.

Phase I and pharmacokinetic study of docetaxel combined with melphalan and carboplatin, with autologous hematopoietic progenitor cell support, in patients with advanced refractory malignancies.

The purpose of this study was to define the maximal tolerated dose (MTD), extramedullary toxicities, and pharmacokinetics of docetaxel combined with high-dose melphalan and carboplatin with autologous hematopoietic progenitor cell support. Fifty-nine patients with advanced refractory malignancy (32 breast cancer, 10 non-Hodgkin lymphoma, 6 germ cell tumors, 4 Hodgkin disease, 4 ovarian cancer, 2 sarcoma, and 1 unknown primary adenocarcinoma) with a median of 3 prior chemotherapy regimens and a median of 3 organs involved were enrolled. Treatment included docetaxel (150-550 mg/m2 infused over 2 hours on day -6), melphalan (150-165 mg/m2 infused over 15 minutes from day -5 to -3), and carboplatin (1000-1300 mg/m2 as a 72-hour continuous infusion from day -5).

Conditioning therapy with intravenous busulfan and cyclophosphamide (IV BuCy2) for hematologic malignancies prior to allogeneic stem cell transplantation: a phase II study.

Busulfan (Bu) is commonly used as a component of conditioning regimens for hematopoietic stem cell transplantation. Precise delivery of the oral formulation is compromised by erratic gastrointestinal absorption. An IV Bu formulation was developed to provide dose assurance and complete bioavailability.

Biokinetics of yttrium-90--labeled huBrE-3 monoclonal antibody.

Background: This study reports summary biokinetics for 17 patients treated with huBrE-3 antibody labeled with indium-111 ((111)In) and yttrium-90 ((90)Y) in a Phase I dose escalation trial.

Methods: Patients were infused with huBrE-3 antibody conjugated to 1-p-isothiocyanatobenzyl 3-methyl- and 1-p-isothiocyanatobenzyl 4-methyl-diethylenetriamine pentaacetic acid (MX-DTPA). The huBrE-3 was labeled with increasing amounts of (90)Y radioactivity according to the following activity regimen: 10 mCi/m(2), 20 mCi/m(2), 33 mCi/m(2), 50 mCi/m(2), and 70 mCi/m(2).

Prognostic model for relapse after high-dose chemotherapy with autologous stem-cell transplantation for stage IV oligometastatic breast cancer.

Purpose: To study prognostic factors after high-dose chemotherapy (HDC) for patients with stage IV oligometastatic breast cancer.

Patients And Methods: Sixty patients with minimal metastatic disease amenable to local therapy enrolled onto a prospective HDC trial were analyzed for potential prognostic factors. Tumor blocks were retrospectively collected from referring institutions.

Liposomal amphotericin B versus conventional amphotericin B in the empirical treatment of persistently febrile neutropenic patients.

Liposomal amphotercin B was compared with conventional amphotericin B for empirical antifungal therapy in febrile neutropenic patients in a randomized, double-blind, multicentre trial. Using a composite end-point, the two drugs were equivalent in overall efficacy. However, the liposomal amphotericin B treatment group had fewer proven fungal infections, fewer infusion-related side effects and less nephrotoxicity.