Methotrexate is a therapeutic agent used widely for osteosarcoma. We used an extremely sensitive high-performance liquid-chromatography assay to evaluate 112 urine samples obtained from 28 hospital employees during high-dose therapy with methotrexate and during routine care of patients. The highest cumulative urinary excretion was observed when methotrexate infusions were handled in a workbench from which a portion of filtered air was emitted into the room. Remarkable urine contaminations were identified for personnel, including 1 administrative employee who had "stood by" for 2 h in the room where infusions were prepared. Lower methotrexate concentrations were detected in the urine of nurses whose exclusive function was to care for patients. The urine burden in oncologic nurses decreased after a central pharmacy unit was installed. Methotrexate was excreted in the sweat of patients who were under high-dose therapy, and its elimination half-life was 11.1 h (mean maximal concentration = 1.7 micrograms/ml [n = 51). The maximal burden in spontaneous vomit from these patients was 441.5 micrograms/ml, and it declined to 0.24 micrograms/ml 19.5 h after infusion was completed. No methotrexate was detected in personnel who prepared 20-g methotrexate infusions in the central pharmacy unit. We demonstrated that occupational safety depended not only on technical precautions, but on the skills of specifically trained personnel.

Antimetabolites, Antineoplastic↗

PubMedDate not supplied

New mucin-like cancer-associated antigens (CA M 26, CA M 29 and CA 549) and a new proliferation marker (TPS) in patients with primary or advanced breast cancer.

In patients with breast cancer no tumor markers giving satisfactory results have been found yet. The aim of our investigation was to compare the usefulness of newly developed tumor markers with the most common used carcinoembryonic antigen and cancer antigen (CA) 15-3. We evaluated the concentrations of carcinoma-associated antigen (CA) 549, carcinoma-associated mucin antigen (CA M) 26 and CA M 29, and the proliferation markers tissue polypeptide antigen (TPA) and tissue polypeptide-specific antigen (TPS) in 84 breast cancer patients with disease progression and in 69 patients with no evidence of disease after surgery for breast cancer. Using receiver-operating characteristic curves (ROC curves) we were able to demonstrate increased sensitivity and specificity of all tested tumor markers in patients with metastatic disease compared with local disease. In our investigation TPA is superior to TPS in all disease states. In local disease, none of the tested markers shows satisfying results. In metastatic disease, the new mucin markers CA M 26 and CA M 29 show slightly better results than CA 15-3 although their ROC curves are nearly congruent. CA 549 is exceeded by the other mucin markers. The best results in this investigation were obtained with CA M 29. The overall results concerning the detection of small tumor masses (i.e. local disease) were unsatisfactory.

Adult↗

PubMedDate not supplied

Prospective randomized clinical trial of primary treatment in breast cancer stages T3/4, N+/-, MO. Chemotherapy vs. radiotherapy. Arbeitskreis für Perioperative Chemotherapie.

209 patients entered a randomized trial. We compared a) pre- and postoperative chemotherapy (= treatment A) [5-drug combination chemotherapy+tamoxifen] versus b) pre- and postoperative radiotherapy (= treatment B). Nonresponders to preoperative chemotherapy were << crossed over >> to postoperative radiotherapy. The study was started in 1983. We now report on 8 years of results. The reduction in tumor size following preoperative treatment was comparable in both legs of the study. No differences were seen with regard to the response of patients with primary tumors or axillary lymph node involvement. Remission rates for treatments A and B were around 60%. In isolated cases the extent of mastectomy could be reduced as a result of preoperative treatments (breast conserving surgery was done in selected cases). While the initially large tumor size often defied even an extended radical operation, the tumor reduction achieved by prior treatment permitted the removal of macroscopically visible tumor tissue by radical surgery using Rotter's procedure. Relapse-free survival (RFS) and overall survival (OAS) on chemotherapy (N = 76) proved to be significantly superior in treatment A (chemotherapy) compared to B (radiotherapy) (N = 75) [(p for A:B RFS = 0.018) (p for A:B OAS = 0.047)]. RFS for << responders >> to chemotherapy was 65% (N = 47) and only 20% (N = 29) for non-responders (p responders vs. non-responder = 0.005). OAS for responders in group A was 79%, and for non-responders 24% (p = 0.005). OAS in group B (radiotherapy) was only 25%. (p A:B = 0.047).

Breast Neoplasms↗