An Attempt to Quantitate "Value" In Medical Oncologic Therapy.

Objective We wanted to examine the incremental cost-effective ratio (ICER) for a variety of Food and Drug Administration (FDA) approved oncology drugs in the adjuvant or curative setting to determine the value provided. Design We examined the annualized incremental drug costs of a variety of FDA approved chemotherapeutic drugs used in an adjuvant or curative setting based on National Comprehensive Cancer Network (NCCN) category 1 practice guidelines for melanoma, Her2/neu over-expressive breast cancer, renal cell carcinoma, stage IIIA non-small cell lung cancer, myeloma, B cell lymphoma, and Hodgkin lymphoma. The studies we examined were randomized clinical trials on which the NCCN guidelines are based; we solely examined the incremental cost-effectiveness of the trial drug as we assumed that the costs of the health care provided were equivalent between the two treatment arms.

Copper deficiency mimicking myelodysplastic syndrome.

Copper deficiency is a rare cause of pancytopenia that may be mistaken for myelodysplastic syndrome. Cytoplasmic vacuolization in erythroid and myeloid precursors is found on bone marrow examination. Patients with a history of abdominal surgery who present with anemia and neutropenia with dysplastic changes should have copper levels checked.

Lenalidomide monotherapy in chemotherapy-naive, castration-resistant prostate cancer patients: final results of a phase II study.

Background: We investigated the activity of lenalidomide, which has antiangiogenic, antineoplastic, and immunomodulatory properties, in chemotherapy-naive, castration-resistant prostate cancer (CRPC) patients.

Patients: Patients received 25 mg/d lenalidomide for 21 days in 28-day cycles, until disease progression or unacceptable toxicity developed. Endpoints included overall response rate and clinical benefit (overall response + stable disease), toxicity, time to radiographic progression, and time to prostate-specific antigen (PSA) progression, overall survival, and quality of life.

Role of sorafenib in overcoming resistance of chemotherapy-failure castration-resistant prostate cancer.

Background: Sorafenib promotes apoptosis through downstream pathways that can be deregulated in CRPC. We hypothesized that sorafenib could overcome chemotherapy resistance in CRPC.

Patients And Methods: Eligible patients were those whose disease had progressed during chemotherapy (docetaxel or mitoxantrone) or within 12 weeks of stopping either.

A phase II study evaluating the toxicity and efficacy of single-agent temsirolimus in chemotherapy-naïve castration-resistant prostate cancer.

Background: The mammalian target of rapamycin (mTOR) pathway is deregulated in castration-resistant prostate cancer (CRPC). We investigated the efficacy and toxicity of temsirolimus, an mTOR inhibitor, in chemotherapy-naïve CRPC.

Methods: In this phase II open label study, eligible patients received IV temsirolimus at 25 mg weekly until objective disease progression, unacceptable toxicity or investigator's discretion.

Phase I study investigating the safety and feasibility of combining imatinib mesylate (Gleevec) with sorafenib in patients with refractory castration-resistant prostate cancer.

Background: Determining the maximum tolerated dose (MTD) and the dose-limiting toxicity (DLT) of sorafenib (S) plus imatinib (IM) in castration-resistant prostate cancer (CRPC) patients.

Methods: Refractory CRPC patients were enrolled onto this 3+3 dose escalation designed study. Imatinib pharmacokinetics (PK) were determined on day 15, 4 h post dose with a validated LC-MS assay.

A phase II pilot trial investigating the efficacy and activity of single agent granulocyte macrophage colony-stimulating factor as maintenance approach in castration - resistant prostate cancer patients responding to chemotherapy.

Purpose: To investigate the toxicity and efficacy of GM-CSF in castration-resistant prostate cancer (CRPC) patients who maximized their response to systemic chemotherapy.

Materials And Methods: CRPC patients who maximized their response to either docetaxel or mitoxantrone chemotherapy were eligible if they demonstrated adequate performance status, liver, kidney, and bone marrow function. Maximum response to chemotherapy was defined as either receiving at least 8 cycles of chemotherapy without radiographic or biochemical progression, receiving less than 8 cycles as long as the prostate-specific antigen (PSA) changes by less than 10%, or being off chemotherapy for less than 12 weeks without disease progression.

Erlotinib has moderate single-agent activity in chemotherapy-naïve castration-resistant prostate cancer: final results of a phase II trial.

Objectives: To investigate the efficacy and toxicity of single-agent erlotinib in chemotherapy-naive castration-resistant prostate cancer.

Methods: Eligible patients received erlotinib at 150 mg daily until disease progression. Toxicity was assessed every 2 weeks and responses every 8 weeks.

A multi-institutional phase II trial of a novel inpatient schedule of continuous interleukin-2 with interferon alpha-2b in advanced renal cell carcinoma: major durable responses in a less highly selected patient population.

Background: A prospective multi-institutional phase II trial was undertaken to define the activity and toxicity of a unique decrescendo infusion of interleukin-2 (IL-2) in combination with interferon (IFN) in patients with metastatic renal cell carcinoma. The identical regimen has shown promise in advanced melanoma.

Patients And Methods: Between February 1997 and March 1999, 47 patients with metastatic renal cell carcinoma, from five institutions, were treated with outpatient s.

Intermittent Androgen Suppression as a Treatment for Prostate Cancer: A Review.

Prostate cancer continues as the most common malignancy in men in the United States, with a large number of patients presenting with advanced disease. The current treatment for metastatic prostate cancer, permanent androgen withdrawal, is palliative. Patients treated with permanent androgen withdrawal usually relapse and die secondary to prostate cancer's ability to progress to an androgen-independent state of growth.

Combination of chemotherapy with interleukin-2 and interferon alfa for the treatment of metastatic melanoma.

Purpose: The primary objective of this clinical study was to assess the feasibility of administering recombinant interleukin-2 and recombinant interferon alfa-2a before and after combination cytotoxic chemotherapy. After encouraging initial responses, the study was expanded to further evaluate the therapeutic potential, clarify the toxicities of this regimen, and explore any associated immunologic changes.

Patients And Methods: Eighty-four patients with metastatic melanoma, including patients with brain metastases, were treated on this 6-week protocol.

Pharmacokinetic and pharmacodynamic evaluation of the topoisomerase inhibitor irinotecan in cancer patients.

Purpose: We conducted a pharmacokinetic and pharmacodynamic evaluation of irinotecan (CPT-11) and determined the effect of race and sex on disposition and toxicity of CPT-11. We tested the efficacy of acetaminophen (AAP) to phenotype SN-38 glucuronidation.

Patients And Methods: Forty patients received a dose of 145 mg/m2 of CPT-11 as a 90-minute infusion.

Etoposide combined with interferon alfa-2b: novel exploitation of established etoposide pharmacokinetics and pharmacodynamics.

Purpose: To construct an efficient pilot study design to determine whether interferon alfa-2b modifies the pharmacokinetics and pharmacodynamics of continuous-infusion etoposide.

Patients And Methods: A two-stage randomized 2 X 2 factorial design was used to evaluate interferon alfa-2b at two doses (2 or 10 MU/m2/day SQ for 3 days) and two schedules (interferon alfa-2b administered before or concurrent with 72-hour continuous-infusion etoposide). Etoposide was administered at 75, 100, or 125 mg/m2/day.

Metabolic fate of irinotecan in humans: correlation of glucuronidation with diarrhea.

Irinotecan (7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxy-camptotheci n (CPT-11) is hydrolyzed by the enzyme carboxyl esterase to 7-ethyl-10-hydroxycamptothecin (SN-38), which further undergoes glucuronic acid conjugation to form the corresponding SN-38 glucuronide (SN-38G). SN-38 is believed to be the cause of treatment-related diarrhea, a dose-limiting toxicity of CPT-11 observed in phase I clinical trials. This study investigated the effect of glucuronidation on the concentrations of SN-38 following CPT-11 infusion in 21 patients undergoing a phase I trial.

Philadelphia chromosome-positive acute lymphoblastic leukemia.

The Philadelphia (Ph1) chromosome, ubiquitous in chronic myelogenous leukemia, also is commonly seen in acute lymphoblastic leukemia, particularly in adults. Whereas the presence of the Ph1 chromosome is associated with high white blood cell count and older age, the Ph1 chromosome is known to be an independent poor prognostic factor. Most Ph1+ patients are able to achieve remissions with intensive, systemic chemotherapy, but treatment is complicated by early relapse.