Eddie Hu

Active-specific immunotherapy for melanoma.

Active specific immunotherapy, or the use of tumor vaccines, attempts to stimulate the patient to reject his or her tumor. Nowhere has this approach been utilized more than in melanoma, often with encouraging results. The best results have occurred in the setting of minimal residual disease after resection of the primary tumor and involved lymph nodes, but responses have also been obtained in disseminated disease. Prolonged survivals of several years have been achieved in both settings, particularly the former, with little toxicity attributable to the treatment. Genetic and biochemical approaches promise considerably improved preparations of vaccines, with defined components and improved activity within the immediate future.

Immunoglobulin gene rearrangements in Hodgkin's disease

An initial survey of biopsy specimens from 16 cases of Hodgkins disease revealed clonal immunoglobulin gene rearrangements in one specimen, which contained large numbers of Reed-Sternberg (R-S) cells. As a result of this finding, the configuration of immunoglobulin and T-cell receptor gene DNA was investigated in biopsy tissues from other cases that were histologically and immunophenotypically consistent with Hodgkins disease and contained numerous R-S cells. In six of seven such specimens (all of the nodular sclerosing subtype), selected solely on the basis of high R-S cell content and sufficient frozen tissue for study, at least one immunoglobulin gene was found to be rearranged in a clonal manner. Additionally, tissue samples obtained at two different time points from the original patient who showed immunoglobulin gene rearrangements revealed identical patterns of rearrangement. In the majority of cases, only a single gene showed rearrangement, and the rearranged bands in Southern blot autoradiograms were usually considerably less intense than the germline bands. No rearrangements of T-cell receptor DNA were detected in any case with a probe for the beta T-cell receptor gene. The results suggest that clonal cell populations possessing uniform immunoglobulin gene rearrangements are present in tissue in some cases of Hodgkins disease. It is not possible to determine which cells contain these rearranged genes, but the increased incidence of detectable rearrangements in cases with high numbers of R-S cell raises the possibility that immunoglobulin gene rearrangement occurs in these cells.

Acute hepatic injury after the withdrawal of immunosuppressive chemotherapy in patients with hepatitis B

Five patients with lymphoproliferative malignancies and chronic hepatitis B suffered severe acute hepatic injury after the withdrawal of multiagent chemotherapy that included high‐dose corticosteroid. Four patients died of hepatic failure, three of whom received corticosteroid as treatment for the hepatic injury. We believe that the cause of this entity is massive immune‐associated cytolysis of hepatitis B virus infected hepatocytes occurring after a period of immunosuppression and increased viral replication. The literature regarding this complication of chemotherapy and its pathophysiology is reviewed.

Follicular and diffuse mixed small-cleaved and large-cell lymphoma--a clinicopathologic study.

The clinical records and initial biopsy materials from 76 patients with mixed small-cleaved and large-cell lymphoma containing both a follicular and diffuse architectural pattern were reviewed. The characteristics of this group, treated at Stanford University Medical Center (SUMC) between 1963 and 1983, are described. The 5-year actuarial survival and freedom from progression are 70% and 27.5%, respectively. Classification according to the degree of follicularity indicated that patients with focally follicular areas (ie, less than 25% of the histologic section) have a significantly worse freedom from progression and overall survival at 5 years compared with those patients with a predominantly follicular architecture (ie, greater than 50% follicular areas). Based on our analysis, we feel that the degree of follicularity is an important prognostic factor and that mixed lymphoma patients with only focally follicular areas behave more like an intermediate-grade lymphoma and should be treated aggressively.

Phase I toxicity and pharmacology study of trimethylcolchicinic acid in patients with advanced malignancies

SummaryA phase I study of trimethylcolchicinic acid (TMCA) given orally once daily for 5 days every 3rd week was performed in 19 patients with advanced malignancies. Myelosuppression and mucositis were the major toxicities observed. Serum TMCA levels were monitored and appear to be useful in predicting toxicities. A partial response was seen in one lymphoma patient and stabilization of disease was noted in one patient each with prostatic and ovarian cancer.

Abstract 4664: Result of TORI L-03, a randomized, multicenter phase II clinical trial of erlotinib (E) or E + fulvestrant (F) in previously treated advanced non-small cell lung cancer (NSCLC).

Background: EGFR inhibition is an established therapy for previously treated NSCLC. Estrogen receptors (ER) and aromatase are expressed in most NSCLC specimens in both men and women. In preclinical models, estrogen stimulates NSCLC growth, an effect blocked by F, a pure ER antagonist. Preclinical models show enhanced anti-tumor effects by combining EGFR inhibitors with F. Methods: We conducted a Phase II clinical study to evaluate whether addition of F enhances antitumor efficacy of E. Men and women with advanced NSCLC and > 1 prior chemotherapy regimen (unless patient refused) were randomized 2:1 to receive E (150 mg PO qd) + F (500 mg IM q2wk x 3, then q4wk) or E alone. Stratification for gender and ECOG (0, 1 vs. 2) was performed. Response rate (RR) was the primary endpoint. Secondary endpoints included progression free survival (PFS), overall survival (OS) and correlation between clinical endpoints and tumor tissue and blood-based biomarkers. Results: 106 patients (pts) were randomized from March 2006 to June 2010. 100 (evaluated population) received E +/- F. E + F was well tolerated, with adverse events well balanced between arms. For E + F and E respectively, RR (23.6% vs. 14.8%, p = 0.35), PFS [1.9 vs. 1.8 months, hazard ratio (HR) 0.85, 95% confidence interval 0.55, 1.33] and OS [9.4 vs. 5.7 months, HR 0.96 (0.6, 1.55)] were similar between arms. EGFR mutational data could be obtained on 69 pts. EGFR mutations were more prevalent in the E arm (35% vs. 20%). EGFR mutations strongly predicted best response, PFS and OS (p Conclusion: E + F was well tolerated in previously treated NSCLC pts, including men and pre- and post-menopausal women. The study showed a high RR (23.6%) for E + F, that was not adequately explained by EGFR mutations. Among EGFR WT pts, a significantly higher CBR that included 3 PRs was seen with trends towards improved PFS and OS with E + F as compared to E alone. Evaluation of tumor tissue biomarkers (including ER-α and -β, aromatase), blood estrogen levels and EGFR ligands known to be induced by ER signaling is ongoing to determine NSCLC subpopulations most likely to benefit from antiestrogens. [Supported by 1K23CA149079, P50 CA090440, V Foundation for Cancer Research, Jonsson Comprehensive Cancer Center, Wolfen Family Lung Cancer Research Program, Stiles Program in Oncology, National Lung Cancer Partnership and One Ball Matt Memorial Golf Tournament] Citation Format: Edward B. Garon, Jill M. Siegfried, Steven M. Dubinett, Robert M. Elashoff, David J. Park, Rupesh J. Parikh, Ravi Patel, Eddie H. Hu, Karen L. Reckamp, Brad Adams, Diego Martinez, He-Jing Wang, Fairooz Kabbinavar, Sanja Dacic, Meghan Brennan, Isett Laux, Diana C. Marquez-Garban, Laura P. Stabile, Dennis J. Slamon, Richard J. Pietras. Result of TORI L-03, a randomized, multicenter phase II clinical trial of erlotinib (E) or E + fulvestrant (F) in previously treated advanced non-small cell lung cancer (NSCLC). [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4664. doi:10.1158/1538-7445.AM2013-4664