Health Hazard Evaluation Report, HETA-98-0052-2820, MD Anderson Cancer Center, Houston,Texas.
On November 25, 1997, the National Institute for Occupational Safety and Health (NIOSH) received a management request for a health hazard evaluation (HHE) at the MD Anderson Cancer Center in Houston, Texas. This request asked NIOSH to evaluate the efficacy of exposure controls during the administration of an experimental antineoplastic agent, 9-nitrocamptothecin (9-NC), to cancer patients, as an aerosol through breathing treatments. No worker health problems were reported in the request; the researchers were interested in evaluating the potential for exposure to health care workers during administration of the drug. During the NIOSH evaluation, experimental work was in the clinical trial stage, and the doses and administration method were agreed upon by the Food and Drug Administration (FDA) as part of their approval process. NIOSH investigators conducted a site visit to the MD Anderson Cancer Center on September 22, 1998, to review the process and determine an appropriate evaluation strategy. At this time, FDA approval to administer 9-NC to cancer patients had not been granted. On August 30, 1999, a return site visit was conducted to collect air samples during the use of 9-NC; low doses of 9-NC were being administered to one patient. Air sampling problems, however, invalidated the results and a return visit was conducted on August 15-16, 2000. During this site visit, area and personal breathing zone (PBZ) air samples for dilauroylphosphatidylcholine (DLPC), a surrogate indicator of 9-NC, were collected. The ventilation system was assessed, and particle monitoring was conducted. This report contains the findings of the August 15, 2000, site visit. During the air monitoring, there were three ventilated patient containment tents in a separately ventilated treatment room operating under negative pressure. Each isolation tent contained the entire treatment ensemble and a chair for the patient. On both days sampled, there were two sets of treatments, with different patients for each set. Detectable concentrations of DLPC were found on area samples collected both inside (41 nanograms per liter [ng/l]) and outside (29.2 ng/l) the treatment tent during the second set of treatments on August 15, 2000. On both days sampled, detectable DLPC was measured inside the treatment tent from the same patient. DLPC was not detected in the treatment room outside the treatment tent during the first set of treatments on August 15, 2000, or during any treatments on August 16, 2000. No DLPC was detected in either of the PBZ samples collected from the treatment administrator or area samples outside the treatment room. Exposure criteria for 9-NC or DLPC has not been established and assessing the health consequences of exposure to the concentrations measured is not possible. Although only limited data was obtained, the particle monitoring conducted during the second set of treatments on both days also showed relatively higher numbers of particles 1.0 micrometers in diameter ( md). The detected DLPC and higher particle numbers can probably be attributed to patient activity; the patient undergoing treatment during the time period DLPC was detected, was active, frequently spoke, and occasionally lifted the treatment tent skirt. The ventilation controls and containment system appear to be adequate, but must be used properly to ensure proper function and that emissions are contained. Surface contamination and the potential exposure of other personnel (e.g., hospital pharmacists) involved in the preparation of the 9-NC liposome were not evaluated during this project. Additionally, the MD Anderson researchers are developing a compassionate (home treatment) system for delivery of the anticancer treatment. Home treatment will present different issues that must be evaluated from a health and safety standpoint. The type of containment and ventilation device, adequacy of facilities, housekeeping, room ventilation, equipment maintenance, and agent storage will vary considerably. Training of personnel responsible for administering the drug to ensure it is handled and disposed of properly will be very important. Under the conditions evaluated, the air monitoring results indicate the delivery and containment system used for the 9-NC treatments effectively control emissions to below detectable limits when patient activity during treatments is limited and the containment system is kept intact. Low airborne levels of DLPC were measured inside and outside the containment tent during treatments involving a patient who was active and talking. No measurable DLPC was detected outside the treatment room, indicating the ventilation system on the containment device, and the room ventilation were adequate to control emissions. Exposure criteria for DLPC or 9-NC has not been established. Surface contamination of 9-NC was not assessed during this project and the impact of increasing the 9-NC dose was not evaluated. A home treatment system will require additional evaluation to ensure all safety and health issues associated with this use are adequately addressed.