Phase I/II study of inhaled doxorubicin combined with platinum-based therapy for advanced non-small cell lung cancer.

Purpose: We have shown the feasibility of administering inhaled doxorubicin to patients with cancer. This study evaluated inhaled doxorubicin combined with cisplatin and docetaxel in patients with non-small cell lung cancer. The principal objective was to determine safety and, secondarily, efficacy.

Phase 1 study of aflibercept administered subcutaneously to patients with advanced solid tumors.

Purpose: To determine the maximum tolerated dose or maximal administered dose and pharmacokinetic and safety profiles of s.c. administered vascular endothelial growth factor Trap (aflibercept), a novel antiangiogenic agent.

Phase II study of cisplatin plus etoposide and bevacizumab for previously untreated, extensive-stage small-cell lung cancer: Eastern Cooperative Oncology Group Study E3501.

Purpose: To investigate the efficacy and safety of bevacizumab plus cisplatin and etoposide in patients with extensive-stage disease, small-cell lung cancer (ED-SCLC).

Patients And Methods: In this phase II trial, 63 patients were treated with bevacizumab 15 mg/kg plus cisplatin 60 mg/m(2) and etoposide 120 mg/m(2), which was followed by bevacizumab alone until death or disease progression occurred. The primary end point was the proportion of patients alive at 6 months without disease progression (ie, progression-free survival [PFS]).

Phase II trial of docetaxel-irinotecan combination in advanced esophageal cancer.

Background: Preclinical evidence suggests synergy between docetaxel and irinotecan, two drugs active in esophagogastric cancer. We previously demonstrated the safety of docetaxel 35 mg/m2 and irinotecan 50 mg/m2 given on days 1 and 8 of a 21-day schedule.

Materials And Methods: Patients who had unresectable/metastatic squamous cell carcinoma or adenocarcinoma of the esophagus, measurable disease, Eastern Cooperative Oncology Group performance status of zero to two, and normal bilirubin were eligible.

Surface-enhanced Raman spectral measurements of 5-fluorouracil in saliva.

The ability of surface-enhanced Raman spectroscopy (SERS) to measure 5-fluorouracil (5-FU) in saliva is presented. The approach is based on the capacity of Raman spectroscopy to provide a unique spectral signature for virtually every chemical, and the ability of SERS to provide microg/mL sensitivity. A simple sampling method, that employed 1-mm glass capillaries filled with silver-doped sol-gels, was developed to isolate 5-FU from potential interfering chemical components of saliva and simultaneously provide SERSactivity.

CTGF, intestinal stellate cells and carcinoid fibrogenesis.

Aim: To investigate the role of small intestinal carcinoid tumor-derived fibrotic mediators, TGFbeta1 and CTGF, in the mediation of fibrosis via activation of an "intestinal" stellate cell.

Methods: GI carcinoid tumors were collected for Q RT-PCR analysis of CTGF and TGFbeta1. Markers of stellate cell desmoplasia were identified in peritoneal fibrosis by immunohistochemistry and stellate cells cultured from fresh resected fibrotic tissue.

Phase II trial of weekly docetaxel/irinotecan combination in advanced pancreatic cancer.

Background: Docetaxel and irinotecan have activity in pancreatic cancer. The combination of docetaxel and irinotecan is attractive because of preclinical evidence of synergy between the two drugs. We have previously demonstrated the safety of docetaxel 35 mg/m(2) and irinotecan 50 mg/m(2) given on days 1, 8, 15, and 21 of a 35-day schedule.

Perforated viscus in a patient with non-small cell lung cancer receiving bevacizumab.

Bowel metastasis and perforation in patients with non-small cell lung cancer is rare. Bevacizumab has emerged as a new therapy in the treatment of metastatic non-small cell lung cancer. Bowel perforation associated with its use has been described in colon and ovarian cancers.

Phase I study of inhaled Doxorubicin for patients with metastatic tumors to the lungs.

Purpose: To evaluate the toxicity profile of inhalational doxorubicin in patients with malignant disease in the lung.

Experimental Design: The OncoMyst Model CDD-2a inhalation device aerosolizes compounds to particles of 2 to 3 mum and prevents exhaled aerosol from escaping into the environment. Deposition efficiency of inhaled Technetium 99m was used to predict deposition of doxorubicin and calculate dose.

Further delineation of the continuous human neoplastic enterochromaffin cell line, KRJ-I, and the inhibitory effects of lanreotide and rapamycin.

Small intestinal carcinoids (SICs) are the most prevalent gastrointestinal carcinoid and characterized by local invasion metastasis and protean symptomatology. The proliferative and secretory regulation of the cell of origin, the enterochromaffin (EC) cell has not been characterized. The absence of either a pure preparation of normal EC cells or human EC carcinoid cell lines has hindered the development of therapeutic agents.

AQUA and FISH analysis of HER-2/neu expression and amplification in a small cell lung carcinoma tissue microarray.

Aims: Most small cell lung carcinoma (SCLC) patients have metastatic disease at the time of diagnosis and are faced with poor prognosis and limited treatment options. Reports of HER-2/neu gene amplification and overexpression in this malignancy have raised the possibility of applying targeted immunotherapy with trastuzumab, the monoclonal antibody used to treat metastatic breast cancer. However, a review of the studies measuring HER-2/neu gene amplification and protein expression in SCLC reveals discordant results.

Oxaliplatin induces a delayed immune-mediated hemolytic anemia: a case report and review of the literature.

We report a case of a 59-year-old woman with metastatic carcinoma of the ileocecal region who received FOLFOX(oxaliplatin/leucovorin/5-fluorouracil) and bevacizumab therapy and exhibited a partial remission with minimal side effects. She developed a mild self-limited episode of immune-mediated hemolytic anemia during her 16th cycle of chemotherapy, which precluded her from receiving further oxaliplatin. We review the literature on oxaliplatin-induced immune-mediated hemolysis, including its mechanism, presenting symptoms, laboratory features, management, and implications for future therapy.

Evaluation of irinotecan plus paclitaxel in patients with advanced non-small cell lung cancer.

Purpose: We conducted a phase II study to evaluate the efficacy and safety of the combination of irinotecan and paclitaxel in patients with advanced stage non-small cell lung cancer (NSCLC).

Patients And Methods: Patients were eligible if they had histologically confirmed chemotherapy naïve stage IV NSCLC or stage IIIB disease that was not suitable for combined modality therapy. Patients were treated with irinotecan 50 mg/m2 and paclitaxel 75 mg/m2 on days 1 and 8 of a 21-day cycle.

Comparison of health-related quality of life questionnaires in ambulatory oncology.

The purpose of this study is to compare three commonly used health-related quality of life (HR-QOL) questionnaires for their ease of use, accuracy, and patient preference; identify factors related to patient preference; identify differences in patient completion rates; and to identify factors associated with patient completion of these questionnaires. Three psychometrically sound measures, the Symptom Distress Scale (SDS), Medical Outcome Study Short Form-36 (SF-36), and Functional Assessment of Cancer Therapy (FACT), were tested. Seventy-nine patients completed questionnaires in the ambulatory oncology setting.

Severe irinotecan-induced toxicities in a patient with uridine diphosphate glucuronosyltransferase 1A1 polymorphism.

Irinotecan is an analogue of camptothecin, a topoisomerase I inhibitor, that has an important role in the management of advanced colorectal cancer. It is approved as first-line therapy in combination with 5-fluorouracil and leucovorin or as monotherapy in the second-line setting. Its clinical use has been associated with variability in terms of pharmacokinetic behavior and toxicities, especially myelosuppression and diarrhea.

A phase I and pharmacokinetic study of VNP40101M, a new alkylating agent, in patients with advanced or metastatic cancer.

Purpose: VNP40101M is a new alkylating agent that demonstrated broad anti-tumor activity in murine tumor models. A phase I trial was initiated to determine the toxicities, maximum tolerated dose, and pharmacokinetics of VNP40101M by short IV infusion.

Study Design: The starting dose was 3 mg/m(2) every four weeks, and was escalated in successive cohorts as follows: 6, 12, 24, 40, 60, 80, and 100 mg/m(2).

Molecular strategies and 111in-labelled somatostatin analogues in defining the management of neuroendocrine tumour disease: a new paradigm for surgical management.

This manuscript provides a gene-chip examination of gastric ECL cell proliferation in an animal model of neuroendocrine tumour disease. Data that were used to identify molecular targets were then utilised to develop novel therapeutic strategies as appropriate adjuncts to surgery in human disease. Alterations in growth-mediated cell signaling (the AP-1 pathway) and in the cell cycle were identified in ECL cell tumours in the animal model and confirmed in human tumour tissue.

AN-9 (Titan).

Titan is developing AN-9 for the potential treatment of various cancers. AN-9 is a histone deacetylase inhibitor analog of butyric acid that causes apoptosis of cancer cells through signaling cellular differentiation. In March 2001, a phase I/II study involving patients with liver tumors was initiated.

Progress in the therapy of small cell lung cancer.

Small cell lung cancer (SCLC) accounts for approximately 14% of all cases of lung cancer. Combination chemotherapy is the most effective treatment modality for SCLC and recently, several new active drugs have emerged. Combinations of platinum agents with CPT-11 or gemcitabine have been successfully compared in phase III trials against the cisplatin/etoposide standard.

A phase II study of topotecan and cyclophosphamide with G-CSF in patients with advanced small cell lung cancer.

Purpose: We conducted a multicenter phase II study to evaluate the efficacy and safety of the combination of topotecan and cyclophosphamide for patients with advanced small cell lung cancer (SCLC).

Patients And Methods: Patients were eligible if they had newly diagnosed extensive stage SCLC or if they had SCLC that progressed more than three months after completion of the first chemotherapy regimen. Patients were treated every 21 days with cyclophosphamide 600 mg/m2 IV on day 1 and topotecan 1.

Irinotecan and taxane combinations for non small-cell lung cancer.

Based on nonoverlapping toxicity profiles and at least additive cytotoxicity in preclinical models, chemo-therapy regimens have been developed that feature the combination of irinotecan and a taxane drug. In the first study, the optimal doses of paclitaxel and irinotecan were 75 mg/m2 and 50 mg/m2, respectively, when chemotherapy was administered weekly for 4 consecutive weeks, followed by a 2-week rest. The dose-limit-ing toxicity for this regimen was neutropenia, and the most prominent nonhematologic toxicities were mild diarrhea and fatigue.

Angiogenesis in non-small cell lung cancer. A new target for therapy.

Non-small cell lung cancer (NSCLC) is cured with surgery in a minority of affected persons. Chemotherapy and radiation can palliate and extend survival of patients with disease not amenable to surgery. Consequently, new treatment options are urgently needed.

Lapatinib ditosylate GlaxoSmithKline.

Lapatinib ditosylate, an ErbB-2 and EGFR dual tyrosine kinase inhibitor, is being developed by GlaxoSmithKline plc for the potential treatment of solid tumors.