PubMed Health⌕ Search

Biomedical subjects

Stan Kaye

Publications and source records attributed to Stan Kaye.

10 recordsLinked to original sources
PubMed2006

Ovarian clear cell adenocarcinoma: a continuing enigma.

Ovarian clear cell adenocarcinomas (OCCAs) account for <5% of all ovarian malignancies. Compared to other epithelial ovarian cancer (EOC) subtypes, when at an advanced stage, they are associated with a poorer prognosis and are relatively resistant to conventional platinum-based chemotherapy. By contrast, early-stage clear cell ovarian cancer carries a relatively good prognosis. Hence, there is a need to improve our understanding of its pathobiology in order to optimise currently available treatments and develop new therapeutic strategies. This review summarises the currently available literature regarding the pathogenesis of OCCA, its molecular genetic features and postulated molecular mechanisms that underlie its chemoresistant phenotype. Marked similarities with clear cell carcinomas of the kidney and endometrium have been noted by some investigators, raising interesting possibilities regarding novel therapeutic approaches. Unfortunately, most studies on OCCA have hitherto been hampered by insufficient sample sizes, leaving many key issues unresolved. It is envisaged that in the future, high-resolution genomic and gene-expression microarray studies incorporating larger sample sizes will lead to the characterisation of the key molecular players in OCCA biology, which may potentially lead to the identification of novel targets for therapeutic development.

Adenocarcinoma, Clear Cell↗
PubMed2006

Update on tubulin-binding agents.

The clinical and commercial success of the taxanes and vinca alkaloids resulted in a drive to improve on current formulations and discover new compounds that target the microtubule. These strategies are all aimed at improving on (1) anti-tumour activity, (2) toxicity profile and (3) pharmacology. Drugs undergoing clinical development include the novel semi-synthetic taxane derivatives (DJ-927, XRP6258 and XRP9881), the epothilones, the dolastations, vinflunine and the combretastatin analogues. In several cases, some improvements in tumour response rates have been seen but randomised trials need to be completed before the role of specific novel tubulin-binding agents can be established.

Antineoplastic Agents↗
PubMed2005

Randomized trial of two intravenous schedules of the topoisomerase I inhibitor liposomal lurtotecan in women with relapsed epithelial ovarian cancer: a trial of the national cancer institute of Canada clinical trials group.

PURPOSE: Liposomal lurtotecan (OSI-211) is a liposomal formulation of the water-soluble topoisomerase I inhibitor lurtotecan (GI147211), which demonstrated superior levels of activity compared with topotecan in preclinical models. We studied two schedules of OSI-211 in a randomized design in relapsed ovarian cancer to identify the more promising of the two schedules for further study. PATIENTS AND METHODS: Eligible patients had measurable epithelial ovarian, fallopian, or primary peritoneal cancer that was recurrent after one or two prior regimens of chemotherapy. Patients were randomly assigned to receive either arm A (OSI-211 1.8 mg/m(2)/d administered by 30-minute intravenous infusion on days 1, 2, and 3 every 3 weeks) or arm B (OSI-211 2.4 mg/m(2)/d administered by 30-minute intravenous infusion on days 1 and 8 every 3 weeks). The primary outcome measure was objective response, which was confirmed by independent radiologic review, and a pick the winner statistical design was used to identify the schedule most likely to be superior. RESULTS: Eighty-one patients were randomized between October 2000 and September 2001. The hematologic toxic effects were greater on arm A than on arm B (grade 4 neutropenia, 51% v 22%, respectively), as was febrile neutropenia (26% v 2.4%, respectively). Of the 80 eligible patients, eight patients (10%) had objective responses; six responders (15.4%; 95% CI, 6% to 30%) were in arm A and two responders (4.9%; 95% CI, 1% to 17%) were in arm B. CONCLUSION: The OSI-211 daily for 3 days intravenous schedule met the statistical criteria to be declared the winner in terms of objective response. This schedule was also associated with more myelosuppression than the schedule of OSI-211 administered in arm B.

Adult↗
PubMed2004

The dl1520 virus is found preferentially in tumor tissue after direct intratumoral injection in oral carcinoma.

PURPOSE: dl1520 (also known as Onyx-015) is an E1B-deleted adenovirus designed to selectively lyse p53-deficient cancer cells. Clinical trials involving patients with recurrent squamous cell carcinoma of the head and neck have shown clinical efficacy, but no direct evidence as to the tumor or p53 selectivity of the virus was demonstrated. We wanted to determine whether dl1520 is selective for survival and replication within tumor tissue after direct injection and whether this is determined by p53 status of the tissues. We also wanted to ascertain whether the virus has any macroscopic effect on normal tissue. EXPERIMENTAL DESIGN: An open-label Phase II trial was devised in which a fixed dose of the virus was administered to 15 patients via a direct intertumoral injection before surgery for untreated oral squamous cell carcinoma. The agent was also delivered into an area of adjacent normal buccal mucosa. Specimens of the excised tumor and of biopsies of the injected normal tissue were assessed for viral presence and p53 status. RESULTS: We demonstrated that the virus replicates selectively in tumor as opposed to normal tissue after this direct injection. It was not possible to determine whether this selectivity was p53 related. It was found that dl1520 triggers an early rise in apoptosis levels in injected normal tissues. No adverse effects of viral injection were noted. CONCLUSIONS: This is the first report of injection of dl1520 into previously untreated squamous cell cancer. The data support the concept that dl1520 is replication deficient in normal, compared with cancerous, tissues and has potential as a selective anticancer agent against tumor tissues.

Adenoviridae↗
PubMed2003

A phase I study of ZD0473 combined with paclitaxel for the treatment of solid malignancies.

PURPOSE: ZD0473 is a cytotoxic platinum agent, which in preclinical studies has exhibited synergistic activity when combined with paclitaxel. The aim of this open-label phase I study was to determine the maximum tolerated dose (MTD), safety, and antitumour activity of ZD0473 followed by paclitaxel in patients with refractory solid malignancies. METHODS: Patients received paclitaxel and ZD0473 on day 1 every 3 weeks. Seven dose levels were planned (ZD0473 60-180 mg/m2, paclitaxel 135-175 mg/m2), with dose escalation dependent on the incidence of dose-limiting toxicity. RESULTS: Included in the study were 23 patients who received 76 treatment cycles at dose levels 1 (60 mg/m2 ZD0473, 135 mg/m2 paclitaxel) to 6 (150 mg/m2 ZD0473, 175 mg/m2 paclitaxel). Dose-limiting thrombocytopenia (platelet count <25x10(9)/l) occurred in two of six patients at dose level 6, which defined the MTD. Grade 3/4 haematological toxicities included: anaemia (21.7%), neutropenia (39.1%), thrombocytopenia (34.8%), and leucopenia (34.8%). The most common grade 3/4 non-haematological toxicities included: alopecia (13.0%), pleural effusion (13.0%), somnolence (8.7%), and vomiting (8.7%). Of the 23 patients, 11 (47.8%) had disease stabilization, including 4 with non-small-cell lung cancer (NSCLC) who had a > or =25% reduction in tumour dimensions. CONCLUSIONS: ZD0473 combined with paclitaxel has a manageable tolerability profile and shows some evidence of antitumour activity in patients with NSCLC.

Adult↗
PubMed2003

Improvements in quality of life and disease-related symptoms in phase I trials of the selective oral epidermal growth factor receptor tyrosine kinase inhibitor ZD1839 in non-small cell lung cancer and other solid tumors.

PURPOSE: The feasibility and utility of assessing quality of life (QoL) and disease-related symptoms in patients with advanced cancer have been evaluated in two Phase I clinical trials of p.o. administered ZD1839 ('Iressa'), an epidermal growth factor receptor tyrosine kinase inhibitor, in patients with advanced cancer. EXPERIMENTAL DESIGN: Functional Assessment of Cancer Therapy (FACT) questionnaires, including disease-specific subscales for lung, head and neck, colorectal, prostate, and ovarian cancer, were completed by patients in two open-label, Phase I, escalating multiple-dose safety and tolerability trials. RESULTS: In 157 patients, 92% of whom had received prior therapy, compliance in returning FACT questionnaires was 87% (European/Australian trial) and 57% (United States trial). This did not appear to be influenced by dose level or tumor type. For patients with colorectal, prostate, or ovarian cancer, median QoL [FACT and Trial Outcome Index (TOI)] scores deteriorated over time. In contrast, for patients with non-small cell lung cancer (NSCLC) or head and neck cancer, median FACT and TOI scores did not deteriorate significantly, and in the United States trial, head and neck cancer scores improved significantly over time. In patients with NSCLC, symptom-related scores measured by the Lung Cancer Subscale of FACT-L appeared sensitive to clinical change. CONCLUSIONS: QoL (FACT-L) questionnaires were used successfully in the Phase I clinical trials of ZD1839. They appeared to be a sensitive tool to monitor clinical changes for the five tumor types in these trials and showed that ZD1839 has the potential to improve patients' QoL.

Administration, Oral↗
PubMed2002

Chemotherapy for metastatic breast cancer-report of a European expert panel.

The anthracyclines doxorubicin and epirubicin, and the taxanes paclitaxel and docetaxel, are effective chemotherapeutic agents for the first-line and second-line treatment of metastatic breast cancer, and their clinical use is widespread. However, for women whose disease has progressed despite receiving these drugs, treatment options are limited. These women often have a good performance status, and may survive for many months or even years, so they should be given the opportunity to benefit from further chemotherapy. The goals of chemotherapy in these patients are to obtain maximum control of symptoms, prevent serious complications, and increase survival without diminishing quality of life. Several agents are used for this purpose, including fluorouracil, docetaxel (in patients who have already received paclitaxel), vinorelbine, and mitomycin c, but because data from controlled trials are limited, a standard regimen has not yet been established. Moreover, these agents may be inconvenient to administer and can be associated with adverse events requiring hospitalisation. Therefore, there is a clear need for additional therapeutic options for patients with metastatic breast cancer. Ideally, agents should have a convenient method of administration, eg, oral, and should be suitable for home-based rather than hospital-based therapy. Treatment should control disease in at least 20-30% of patients with an acceptable side-effect profile. Novel oral therapies have now been developed and are being used increasingly in patients whose disease has progressed following taxane therapy.

Antibiotics, Antineoplastic↗