Showing papers by "Aminah Jatoi published in 2006"

A phase I and pharmacologic study of sequences of the proteasome inhibitor, bortezomib (PS-341, Velcade), in combination with paclitaxel and carboplatin in patients with advanced malignancies.

Abstract: Bortezomib, a selective inhibitor of the 20S proteasome with activity in a variety of cancers, exhibits sequence-dependent synergistic cytotoxicity with taxanes and platinum agents. Two different treatment schedules of bortezomib in combination with paclitaxel and carboplatin were tested in this phase I study to evaluate the effects of scheduling on toxicities, pharmacodynamics and clinical activity. Patients with advanced malignancies were alternately assigned to receive (schedule A) paclitaxel and carboplatin (IV d1) followed by bortezomib (IV d2, d5, d8) or (schedule B) bortezomib (IV d1, d4, d8) followed by paclitaxel and carboplatin (IV d2) on a 21-day cycle. Fifty-three patients (A 25, B 28) were treated with a median of 3 cycles (range 1–8) for schedule A and 3.5 cycles (range 1–10) for schedule B. Grade 3 or higher treatment related hematologic adverse events in all cycles of treatment included neutropenia (A 52%, B 50%), anemia (A 12%, B 7.1%) and thrombocytopenia (A 16%, B 17.9%). Non-hematologic treatment related adverse events were fairly mild (primarily grades 1 and 2). The maximum tolerated dose and the recommended doses for future phase II trials are bortezomib 1.2 mg/m2, paclitaxel 135 mg/m2 and carboplatin AUC = 6 for schedule A and bortezomib 1.2 mg/m2, paclitaxel 175 mg/m2 and carboplatin AUC = 6 for schedule B. Six (21.4%) partial responses (PR) were seen with schedule B. In contrast, only 1 (4%) PR was achieved with schedule A. Similar proteasome inhibition was achieved at MTD for both schedules. Administration of sequential bortezomib followed by chemotherapy (schedule B) was well tolerated and associated with an encouraging number of objective responses in this small group of patients. Further studies with this administration schedule are warranted.

The proteolysis-inducing factor: in search of its clinical relevance in patients with metastatic gastric/esophageal cancer.

Abstract: SUMMARY. The proteolysis-inducing factor is a putative mediator of cancer-associated weight loss. The goal of this study was to examine for the first time: (i) its prevalence in patients with metastatic gastric/esophageal cancer; and (ii) whether it possibly correlated with weight loss and anorexia and whether it predicted tumor response and patient survival. This study recruited 41 patients as part of a phase II therapeutic, chemotherapy protocol for patients with metastatic gastric/esophageal cancer. Patient eligibility criteria were designed to select a group of patients who would tolerate treatment with the drugs capecitabine and oxaliplatin. Urine for assaying the proteolysis-inducing factor was obtained at registration and then 6 weeks later. Patients completed the FACT-E questionnaire every 6 weeks and had their weights checked at the same interval. Patients were followed prospectively for tumor response and patient survival. Twenty-three (56%) patients had the proteolysis-inducing factor in their urine at registration, and 18 (64%) had it at 6 weeks. There was no statistically significant correlation between the presence of the proteolysis-inducing factor and weight loss or between its presence and anorexia. Moreover, there was no evidence that the presence of the proteolysis-inducing factor in urine was able to predict tumor response or patient survival. The proteolysis-inducing factor in urine does not appear to be tied to weight loss, anorexia, tumor response, or patient survival in the clinical setting of metastatic gastric/esophageal cancer.

Pharmacologic therapy for the cancer anorexia/weight loss syndrome: A data-driven, practical approach.

Abstract: The cancer anorexia/weight loss syndrome occurs in over 80% of patients with incurable cancer and is associated with a poor prognosis and negative effects on quality of life Educating patients and families plays an important role in its management, and caregivers sometimes forget that in select patients who are candidates for it, antineoplastic therapy can occasionally reverse some aspects of this syndrome Patients may also benefit from appetite stimulants such as corticosteroids and progestational agents,and this review summarizes the benefits of using these agents as well as their contraindications

Curing patients with locally advanced esophageal cancer: an update on multimodality therapy

Abstract: SUMMARY. Combining different treatment modalities – such as surgery, radiation, and chemotherapy – is often utilized to treat patients with locally advanced esophageal cancer. However, it remains controversial how best to combine these modalities to provide patients with the greatest chance of cure. This review discusses recent studies in this field and outlines promising versus less promising therapeutic strategies.

Can complementary and alternative medicine clinical cancer research be successfully accomplished? The Mayo Clinic-North Central Cancer Treatment Group experience.

Abstract: Some critics question whether research on complementary and alternative modalities for patients with cancer can be done efficiently in traditional clinical settings. This article reviews a program of complementary medicine research that has been done in a traditional clinical setting over the past 30 years. Trials using complementary therapies for both symptom management and cancer treatment done by the Mayo Clinic and the North Central Cancer Treatment Group are reviewed. Twenty-seven studies have been developed using complementary therapies, addressing such issues as mucosal and epidermal toxicity, hot flashes, lymphedema, anorexia and cachexia, insomnia, cognitive dysfunction, fatigue, and cancer treatment. Nineteen of them have been completed and have had results published in peer-reviewed clinical journals, whereas two manuscripts are in press. Two other trials have recently completed accrual, and the data are being analyzed so that manuscripts can be prepared. In addition, four clinical trials are actively accruing patients. The data presented in this article demonstrate that complementary and alternative medicine research can be done in a scientifically sound manner. Well-designed and adequately powered studies can be implemented, and large numbers of patients can be accrued. The resulting research evaluations can be published in peer-reviewed medical journals.

New agents, new rashes: an update on skin complications from cancer chemotherapy.

Abstract: Several new drugs have emerged as effective antineoplastic agents in the past 5 years. Many of these drugs cause rashes. For example, rash is one of the two most frequent adverse events that occur in cancer patients prescribed epidermal growth factor receptor inhibitors. This review discusses rash in the context of epidermal growth factor receptor inhibitors and in the context of a few other recently approved cancer drugs. It also embarks on a brief discussion of issues that investigators must face when designing clinical trials aimed at rash palliation.

Characteristics of long-term lung cancer survivors.

Abstract: Fifth AACR International Conference on Frontiers in Cancer Prevention Research, Nov 12-15, 2006 PR-17 Background. People who survive beyond five years after a lung cancer diagnosis have been referred to as long-term lung cancer (LTLC) survivors. There currently is limited information about the health status, health behaviors, and quality of life (QoL) of LTLC survivors. In our multiple-dimension study, comprehensive models were explored under a conceptual model of Wilson and Cleary (1) to capture the most important survival predictors. Our framework encompasses the following five dimensions: health and QoL (e.g., comorbid conditions and spiritual well-being), health-related behaviors (e.g., smoking status and physical activity level), disease and treatment related factors (e.g., adverse effects and disease recurrence), host related factors (e.g., genotypes of oxidative pathways), tumor related factors (e.g., histology and markers of cell proliferation and apoptosis), as well as demographic variables. Methods. We conducted a matched multivariate analysis to assess predictors for longer survival and better QoL. We sequentially modeled from each study dimension and then to higher order dimensions. LTLC survivors (n=150) were matched to patients who survived less than 2 years (n=150) by known survival predictors including age at diagnosis, gender, tumor cell type, TNM stage, and number of primary lung cancers. Results . Under disease dimension, patients with any progression or recurrence were almost 3 times more likely to die within 2 years than those without progression or recurrence; under treatment dimension, those who had surgery were only 33% as likely to die within 2 years as those without surgery; under physical functioning dimension, patients who reported being "unable to do work or could only do light work" were at a 2.7-5.8 fold higher probability of dying within 2 years than those who were fully active; and under host susceptibility dimension, patients with a GSTM1 positive allele (indicative of a higher anti-oxidative function) were 4 times less likely to die within 2 years than those with a null type. Summary. In this initial analysis, we have shown the importance of all five dimensions, with varying magnitude. New knowledge gained from our study may help lung cancer survivors, their healthcare providers, and their caregivers by providing evidence for establishing clinical recommendations to enhance their long-term survival and health-related QoL. (This study is supported by NIH grants CA77118, CA80127, CA84354, and CA115857.) 1. Wilson IB, Cleary PD. Linking clinical variables with health-related quality of life: A conceptual model of patient outcomes. JAMA 1995; 273:59-65

An Update on Therapeutics: The Cancer Anorexia/Weight Loss Syndrome in Advanced Cancer Patients

Abstract: Experienced oncologists acknowledge that the cancer anorexia/weight loss syndrome predicts a shorter survival for patients with advanced, incurable disease. Several powerful, well-conducted studies have borne out this clinical impression. DeWys et al. focused on weight loss in a multiinstitutional, retrospective review of 3047 cancer patients and observed that loss of more than 5% of premorbid weight predicted an early demise [1]. This prognostic effect occurred independently of tumour stage, tumour histology and patient performance status. Weight loss was also associated with a trend towards lower chemotherapy response rates.