NCI 6896: a phase I trial of vorinostat (SAHA) and isotretinoin (13-cis retinoic acid) in the treatment of patients with advanced renal cell carcinoma.

Preclinical studies suggest that histone deacetylase (HDAC) inhibitors may restore tumor sensitivity to retinoids and have synergistic anti-tumor activity when combined. We performed a Phase I clinical trial to evaluate the safety and preliminary efficacy of combining the oral HDAC inhibitor vorinostat and isotretinoin in patients with advanced renal cell carcinoma (RCC). Vorinostat was administered at 300 mg orally twice daily in combination with escalating doses of isotretinoin for 3 consecutive days per week.

Core Entrustable Professional Activities in Clinical Pharmacology for Entering Residency: Value of Interprofessional Health-Care Teams in Medication Prescribing and Medication Error Prevention.

In recent years, health care has been increasingly delivered by interprofessional teams in the inpatient, outpatient, and transition-of-care arenas. For many reasons, effective communication between patient-centered care teams and patients is critically important in order to optimize care, ensure patient safety, and prevent medical and medication misadventures. In rapid-paced, high-stress medical environments, it is especially important to carefully evaluate the causes of all misadventures in a manner that avoids assigning blame and identifies the root causes and, through team activity, leads to development of remedies that reduce the likelihood of future misadventures.

Occurrence of renal cell carcinoma and hematologic malignancies (predominantly lymphoid) in individuals and in families.

The relationship between renal cell cancer (RCC) and hematologic malignancy (HM) in the same individual has been reported for more than 20 years, and is noted in SEER database studies. Family histories suggest a familial association as well. This study evaluates the occurrence of renal cell cancer and hematologic malignancies in individual patients and families, and the occurrence of age-of-onset anticipation among generations.

Atrasentan in Patients With Advanced Renal Cell Carcinoma: A Phase 2 Trial of the ECOG-ACRIN Cancer Research Group (E6800).

Background: Atrasentan, an oral endothelin receptor A antagonist, demonstrated phase 1 activity in patients with renal cell carcinoma (RCC). A phase 2 study was undertaken in patients with measurable or bone-only metastatic RCC in the pre-VEGF/TKI era.

Methods And Materials: Patients were stratified by disease status and prior immunotherapy.

Effects of Adjuvant Sorafenib and Sunitinib on Cardiac Function in Renal Cell Carcinoma Patients without Overt Metastases: Results from ASSURE, ECOG 2805.

Purpose: Sunitinib and sorafenib are used widely in the treatment of renal cell carcinoma (RCC). These agents are associated with a significant incidence of cardiovascular (CV) dysfunction and left ventricular ejection fraction (LVEF) declines, observed largely in the metastatic setting. However, in the adjuvant population, the CV effects of these agents remain unknown.

Serum CA125 and PSA concentrations in patients with lymphoma.

Serum determinations of CA125 and prostate-specific antigen (PSA) have been useful in monitoring the status of ovarian and prostate cancer, respectively. However, these antigens are not specific for these neoplasms and ignorance of that fact may lead to confusion in certain settings. Serum CA125 can be elevated in many benign and malignant conditions in which coelomic epithelium is involved.

Lenalidomide monotherapy in relapsed or refractory aggressive non-Hodgkin's lymphoma.

Purpose: The major cause of death in aggressive lymphoma is relapse or nonresponse to initial therapy. Lenalidomide has activity in a variety of hematologic malignancies, including non-Hodgkin's lymphoma (NHL). We report the results of a phase II, single-arm, multicenter trial evaluating the safety and efficacy of lenalidomide oral monotherapy in patients with relapsed or refractory aggressive NHL.

A complex pattern of melanonychia and onycholysis after treatment with pemetrexed for lung cancer.

A 53-year-old black man was diagnosed with poorly differentiated adenocarcinoma of the lung and treated initially with 4 cycles of paclitaxel in combination with carboplatin and external-beam radiation therapy with a good clinicoradiologic response. The patient tolerated the chemotherapy well and did not develop any skin or nail changes during that period of time. His lung cancer recurred 10 months later, when he was found to have bone metastases.

Effects of desialylation of ovine submaxillary gland mucin (OSM) on humoral and cellular immune responses to Tn and sialylated Tn.

Resected carcinoma patients were immunized 3-5 times with ovine submaxillary gland mucin (OSM) containing predominantly sialylated Tn (sTn), completely desialylated ovine submaxillary gland mucin (dOSM) containing predominantly Tn, or 50% desialylated OSM containing Tn and sTn plus bacillus Calmette-Guerin (BCG) as an immunologic adjuvant. Pre- and postimmunization sera were quantified by ELISA, whole-cell ELISA, and immune stain dot blots. Fifteen of 17 patients produced IgG antibody titers from 40 to 5120 times more reactive with OSM and dOSM postimmunization.

Phase II study of carboxyamidotriazole in patients with advanced renal cell carcinoma refractory to immunotherapy: E4896, an Eastern Cooperative Oncology Group Study.

Background: The current study evaluated the response rate and 6-month time to disease progression of the antiangiogenesis agent carboxyamidotriazole (CAI) in patients with metastatic renal cell carcinoma (RCC).

Methods: Fifty-seven patients with histologically confirmed metastatic RCC that progressed after biologic therapy (interferon or interleukin-2) were enrolled. Four patients were ineligible.

Phase II study of theophylline in chronic lymphocytic leukemia: a study of the Eastern Cooperative Oncology Group (E4998).

The Eastern Cooperative Oncology Group (ECOG) performed a phase 2 study in B-cell chronic lymphocytic leukemia (CLL) of oral theophylline, a methylxanthine that inhibits cyclic nucleotide phosphodiesterases, thereby inducing the intracellular accumulation of cyclic adenosine monophosphate (cAMP). In 25 patients with Rai stages 0-I, theophylline, 200 mg given orally every 12 h was well tolerated. There was one complete response after 22.

Second neoplasms in patients with chronic lymphocytic leukemia.

Second malignancies occur with increased frequency in patients with chronic lymphocytic leukemia (CLL) regardless of treatment, but they may be more frequent and more aggressive after nucleoside analog therapy of CLL. In as many as 33% of patients with CLL who develop a second malignancy, a spontaneous remission of CLL precedes the diagnosis of the second malignancy by months or years. Richter's syndrome, whether manifested by anaplastic large cell lymphoma or Hodgkin's disease, is not truly a second malignancy because the CLL clone appears to be involved.

A surrogate marker profile for PML/RAR alpha expressing acute promyelocytic leukemia and the association of immunophenotypic markers with morphologic and molecular subtypes.

Background: The availability of genotype-specific therapy for PML/RAR alpha(pos) acute promyelocytic leukemia (APL) requires that this disease be precisely diagnosed. Immunophenotypic characteristics heretofore proclaimed as reliably characterizing APL (HLA-DR(low), CD34(low), P-glycoprotein(low) myeloid phenotype) do not differentiate from APL-like immune profiles unassociated with the PML/RAR alpha fusion transcript.

Methods: To establish a surrogate marker profile for APL, we explored 19 potentially predictive markers compared with differentiated acute myeloid leukemia using the classification tree approach with recursive partitioning.

Activating FLT3 mutations in CD117/KIT(+) T-cell acute lymphoblastic leukemias.

Activating FLT3 mutations are the most common genetic aberrations in acute myeloid leukemia (AML), resulting in the constitutive activation of this receptor tyrosine kinase (RTK), but such mutations are rarely found in acute lymphoblastic leukemia (ALL). Here we describe a unique subset of de novo adult T-cell ALL (T-ALL) cases that coexpress CD117/KIT and cytoplasmic CD3 (CD117/KIT(+) ALL). Activating mutations in the FLT3 RTK gene were found in each of 3 CD117/KIT(+) cases that were analyzed, but not in 52 other adult T-ALL samples from the same series that lacked CD117/KIT expression.

Cardiac monitoring of patients receiving arsenic trioxide therapy.

Arsenic trioxide (ATO) is approved for the treatment of acute promyelocytic leukaemia and is under investigation for other malignancies. We report the cardiac findings in 18 patients with haematologic malignancies treated with ATO and assess the role of cardiac factors in fluid retention syndrome observed during ATO therapy. Based on initial observations in 10 patients treated with ATO, cardiac functions in the subsequent eight patients were evaluated prospectively.

Mammalian target of rapamycin (mTOR) Inhibitors.

Current efforts in anticancer drug development are targeting key factors in cell-cycle regulation. Mammalian target of rapamycin (mTOR) is one such protein kinase that facilitates cell growth by stimulating the cell to traverse the G1 to S phase of the cell cycle. Rapamycin is the first defined inhibitor of mTOR, and the demonstration of its antitumor activity has led to great interest in this pathway as an antitumor mechanism.

Interleukin-2 based therapy for kidney cancer.

In summary, IL-2 based therapy remains the basis for treatment of metastatic renal cell cancer. Un-answered questions remain in the development of regimens that exceed a mean response rate of 20%. Additionally, there may be differences among the histologic subtypes of renal cell cancer that predispose to response or lack there of to immunotherapy, and this is being further explored.

How to optimize multiparameter flow cytometry for leukaemia/lymphoma diagnosis.

Multiparameter flow cytometry can allow for accurate lineage assignment of leukaemia cell populations in approximately 99% of cases, whereby the emphasis lies in the word 'can'. Despite the fact that the very few markers that are lineage-specific are localized inside the cell (e.g.

Stratification by risk factors predicts survival on the active treatment arm in a randomized phase II study of interferon-gamma plus/minus interferon-alpha in advanced renal cell carcinoma (E6890).

Introduction: Standard therapy for recurrent or metastatic renal carcinoma includes the biologic response modifiers interferon-alpha (IFN-alpha) and interleukin-2 (IL-2). The response rate for both agents is modest and toxicity is significant. New agents are needed.

Low expression of the myeloid differentiation antigen CD65s, a feature of poorly differentiated AML in older adults: study of 711 patients enrolled in ECOG trials.

CD65s appears when the progenitor antigen CD34 disappears, suggesting that this sialylated carbohydrate antigen marks a turning point in normal myeloid differentiation. We characterized acute myeloid leukemia (AML) with low CD65s expression (CD65s(low) AML) in 711 patients entered on seven Eastern Cooperative Oncology Group AML treatment trials (1986-1999). Of those, 198 (28%) qualified as having CD65s(low) AML.

The role of Epstein-Barr virus and elevated levels of tumor necrosis factor in determining prognosis in Asian peripheral T-cell lymphomas.

Evidence of Epstein-Barr virus (EBV) infection in patients continues to be associated with the development of various lymphomas, and EBV genomic regions are detected in some lymphoma cells. Its role in causality and progression of disease versus the role of a passenger continues to be debated. Several reports of Asian T-cell lymphomas have also associated these diseases with evidence of EBV infections.

Accelerated and blastic phase of chronic myeloid leukemia.

There is currently no standard treatment for the blastic phase of chronic myeloid leukemia (CML-BC), which is a chemoresistant form of acute leukemia. Current approaches include using standard acute myeloid leukemia (AML) regimens in an effort to induce remission, variations of these approaches with drugs that seem more active in this specific leukemia, and the direct entry of patients into studies of investigational agents. Although the likelihood of achieving remission is small, immediate bone marrow transplantation in remission should be considered because it provides the only opportunity for long-term survival at this time.