Biomedical subjects

Scot C Remick

Publications and source records attributed to Scot C Remick.

21 records · Page 2Linked to original sources

PubMed2003

Administration of oxaliplatin to patients with renal dysfunction: a preliminary report of the national cancer institute organ dysfunction working group.

Oxaliplatin is an approved agent with clinical activity in the treatment of advanced colorectal cancer. Preliminary pharmacokinetic evidence suggests that oxaliplatin is predominantly cleared by renal excretion; however, formal dosing guidelines in patients with renal impairment are lacking. The National Cancer Institute Organ Dysfunction Working Group initiated the following dose-escalation pharmacokinetic trial of oxaliplatin in patients with varying degrees of renal function. Thirty-seven patients with various solid tumor malignancies were stratified into four renal dysfunction groups based on their measured 24-hour urinary creatinine clearance (CrCL). Patients in group A (controls) all had a CrCL >or= 60 mL/min; group B patients had mild renal dysfunction with CrCLs ranging from 40 to 59 mL/min; group C patients had moderate renal dysfunction with CrCLs of 20 to 39 mL/min; and patients with a CrCL < 20 mL/min were entered into the group D severe cohort. The starting oxaliplatin dose for patients in the normal group A was 130 mg/m(2), while lower doses of 105, 80, and 60 mg/m(2) were used in groups B, C, and D, respectively. Patients received a 2-hour intravenous infusion of oxaliplatin every 3 weeks, and doses were escalated in cohorts of three patients in each renal dysfunction group in the absence of any severe dose-limiting toxicity. Oxaliplatin-associated platinum pharmacokinetics were monitored in both plasma (bound + unbound) and plasma ultrafiltrates (unbound). Full single-agent doses of oxaliplatin of 130 mg/m(2) were well tolerated by patients with normal, mild, and moderate renal dysfunction in groups A, B, and C, respectively. Only one patient was enrolled in group D. Unbound platinum clearance significantly correlated with CrCL (r =.884), but the increased systemic exposures to circulating platinum were not associated with increased clinical toxicities. These data suggest that dose reductions of single-agent oxaliplatin are not necessary in patients with CrCLs >20 mL/min.

Adult↗

PubMed2002

A phase I pharmacokinetic and translational study of the novel vascular targeting agent combretastatin a-4 phosphate on a single-dose intravenous schedule in patients with advanced cancer.

Combretastatin A-4 phosphate (CA4P) is a novel antitumor vascular targeting agent, the first agent of this class of compounds to enter the clinic. We performed a Phase I trial to determine the maximum-tolerated dose, safety, and pharmacokinetic profile of CA4P on a single-dose i.v. schedule. We also obtained preliminary data on its effect on tumor blood flow using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) techniques and cell adhesion molecules at the higher-dose levels. Twenty-five assessable patients with advanced cancer received a total of 107 cycles over the following dose escalation schema: 18, 36, 60, 90 mg/m(2) as a 10-min infusion and 60 mg/m(2) as a 60-min infusion at 3-week intervals. There was no significant myelotoxicity, stomatitis, or alopecia. Tumor pain was a unique side effect, which occurred in 10% of cycles, and there were four episodes of dose-limiting toxicity at dosages > or =60 mg/m(2), including two episodes of acute coronary syndrome. Pharmacokinetics revealed rapid dephosphorylation of the parent compound (CA4P) to combretastatin A4 (CA4), with a short plasma half-life (approximately 30 min). A significant (P < 0.03) decline in gradient peak tumor blood flow by DCE-MRI in six of seven patients treated at 60 mg/m(2) was observed. A patient with anaplastic thyroid cancer had a complete response and is alive 30 months after treatment. The toxicity profile is consistent with a drug that is "vascularly active" and devoid of traditional "cytotoxic" side effects. Dosages < or =60 mg/m(2) as a 10-min infusion define the upper boundary of the maximum-tolerated dose.

Adult↗

PubMed2002

Therapeutic challenges of AIDS-related non-Hodgkin's lymphoma in the United States and East Africa.

Non-Hodgkin's lymphoma (NHL) remains the second most common malignant complication in patients with human immunodeficiency virus (HIV) infection. As we enter the third decade of the acquired immunodeficiency syndrome (AIDS) epidemic, it is apparent that the evolution of antiretroviral therapy and the emergence of combination antiviral strategies have greatly affected the natural history of HIV infection and its neoplastic complications. For example, there may be a trend for declining incidence of AIDS-related lymphoma in the United States for the first time. However, in regions of the world where the burden of HIV infection is greatest, such as in East Africa, AIDS-related lymphoma is an increasing cause of morbidity and mortality. Treatment of lymphoma has evolved coincident with improvements in antiretroviral therapy. Infusional chemotherapy regimens may offer advantages over other regimens and schedules, but comparative trials have not been done. Clinical trial data are available on which to develop therapeutic strategies to treat this disease in East Africa where pragmatic approaches are needed. Both the differences in manifestations of HIV infection and the inherent difficulties in administering cytotoxic chemotherapy in this part of the world must be taken into consideration in planning therapeutic strategies. Improved understanding of the pathogenesis of HIV infection and lymphoma will likely yield improved therapeutic interventions as well.

Acquired Immunodeficiency Syndrome↗