Martin D. Abeloff

Biological markers and small cell carcinoma of the lung. A clinical evaluation of urinary ribonucleosides

Five minor base ribonucleosides, primarily degradation products of transfer ribonucleic acid (tRNA), were evaluated as potential biological markers for patients with small cell carcinoma of the lung. The urinary concentration for pseudouridine, 1‐methyladenosine, 1‐methylinosine, N2‐methylguanosine, and N2,N2‐dimethylguanosine was determined by means of reversed‐phase high performance liquid chromatography and quantitatively expressed as a function of creatinine excretion. Comparisons were made with carcinoembryonic antigen (CEA) plasma levels. The total frequency of elevated values for the five nucleosides in pretreatment urine samples was directly related to stage of disease with 24/60 (40%) determinations increased in 12 patients with limited disease and 69/85 (81%) in 17 patients with extensive disease. For these same patients, CEA levels were elevated respectively in 2/11 (18%) of the former and 9/17 (53%) of the latter group. The frequency and degree of elevation of the nucleoside/creatinine ratios in pretreatment samples from patients with extensive disease was correlated directly with increasing number of metastatic sites. Of the five nucleosides, the mean number elevated was two for limited disease, 3–4 for extensive disease with one metastatic site, 4 for two or three, and 5 for four or more sites of metastases. Based on a summation of pretreatment nucleoside/creatinine ratios, a discriminant for survival was derived giving curves separating patients (P = 0.086) similar to the discriminant based on stage of disease. Although discordant results were noted, an overall correlation of 75% agreement with clinical assessment was estimated in response categories when monitoring changes associated with therapy.

Acute leukemia following intensive therapy for small‐cell carcinoma of the lung

Acute leukemia developed in two patients who had been in remission for longer than two years after receiving intensive combination chemotherapy and radiotherapy for small‐cell carcinoma of the lung. Both patients were first seen with pancytopenia and sideroblastic anemia with increased erythroblasts in the bone marrow. Chromosomal abnormalities were demonstrated in both cases. It is likely that the intensive combination therapy given to these patients caused transformation of bone marrow stem cells, resulting in acute leukemia.

Phase I trial and pharmacokinetic study of intravenous and oral α-Difluoromethylornithine

Eflornithine-HCl (α-difluoromethylornithine or DFMO), an irreversible inhibitor of ornithine decarboxylase, blocks polyamine synthesis and has demonstrated antitumor activity in cell culture and animal tumor models. This phase I study was designed to determine and compare toxicity and the maximally tolerated dose of a 4-day course of DFMO given to patients in oral, continuous intravenous infusion or pulse intravenous infusion forms. Twenty-four patients were entered into this study: 8 received intravenous pulse drug, 10 intravenous continuous infusion of drug, and 6 oral DFMO. The most frequent toxicity was nausea and vomiting which occurred in 9 courses of oral drug. Only two patients receiving intravenous DFMO had nausea and vomiting. Clinically significant thrombocytopenia and audiometric abnormalities were not encountered in contrast to previous experience with 28-day courses of oral DFMO. The maximally tolerated dose of a four-day course of oral DFMO was 3.75 gm/M2 every 6 hours. The maximally tolerated dose of intravenous pulse and continuous infusion DFMO was not attained. Pharmacokinetic studies demonstrated that the intravenous schedules achieved higher plasma levels of DFMO than those previously obtained with chronic oral dosing.

Adjuvant therapy in node-negative breast cancer. A panel discussion.

William L. McGuire 1 (moderator), Martin D. Abeloff 2, Bernard Fisher 3, John H. Glick 4, I. Craig Henderson 5 and C. Kent Osborne 1 1 University of Texas Health Science Center, San Antonio TX, 2 Johns Hopkins University School of Medicine, Baltimore MD; ~ University of Pittsburgh School of Medicine, Pittsburgh PA; 4 University of Pennsylvania School of Medicine, Philadelphia PA; 5 Dana Farber Cancer Institute and Harvard Medical School, Boston MA, USA

Serum protein-bound carbohydrates and small cell carcinoma of the lung. Correlations with extent of disease, tumor burden, survival, and clinical response categories

The levels for serum protein bound neutral carbohydrates (fucose, mannose, and galactose) were determined at specific intervals for 40 patients with small cell carcinoma of the lung and compared to the corresponding carcinoembryonic antigen (CEA) levels. In pretreatment samples, the frequency of elevation was 92.5% for fucose and 77.5% each for mannose and for galactose. CEA determined in these same samples was elevated (>5 ng/ml) in 45.0%. One or more of the three carbohydrate levels were elevated in pretreatment serum of 95.0% of the patients. The individual frequency of elevation for each carbohydrate was significantly related to initial stage of disease (P < 0.01). Median survival was significantly longer for patients based on a discriminant of <3 carbohydrates elevated in pretreatment samples (25 months) to all 3 elevated (11 months) with P = 0.0302. A single value, termed the biomarker index, was calculated to represent the summation of the individual carbohydrate levels per individual serum sample. The biomarker index was found to be directly correlated with extent of primary disease, number of metastic sites, tumor burden, and clinical response categories assessed at serial time points. For patients with both low Biomarker Index values and normal CEA levels in pretreatment samples, an initial rise in both determinations occurred frequently corresponding to partial or complete tumor response. The occurrence of such discordant results must be considered as a likely possibility for those patients with low or normal pretreatment biological marker levels and subsequent response to primary chemotherapy. Cancer 52:131‐139, 1983.

Treatment of stage III breast cancer: A panel discussion

A major question in oncology today concerns the most appropriate therapy for locally advanced breast cancer. Realistic goals include effective local treatment and a prolonged disease-free interval for these patients, most of whom have incurable disease. Here, our panel discusses the roles of surgery, radiation therapy, chemotherapy, and hormonal therapy, and the proper sequencing of these modalities.

Herpes Zoster in Small-Cell Carcinoma of the Lung

Excerpt To the editor: The development of herpes zoster is a well-recongized complication of the treatment of Hodgkins and non-Hodgkins lymphomas (1). Recently, two groups of investigators have r...