AnesthesiaWeb - Lit Reviews- Human Chromaffin Cell Graft into the CSF for Cancer Pain Management

Sept 2000

Human Chromaffin Cell Graft into the CSF for Cancer Pain Management: A Prospective Phase II Clinical Study
Lazorthes Y, Sagen J, Sallerin B, Tkaczuk J, Duplan H, Sol J-C, Tafani M, Bès JC

Commentary by Richard W. Rosenquist, M.D.

[see abstract below]

Although the majority of patients with complaints of pain resulting from cancer can be successfully treated using the WHO three-step analgesic-ladder approach, some patients develop intolerable side effects and resistance to adjuvant treatments. In selected patients, the delivery of medications within the spinal fluid allows for a dramatic reduction in required dose and is associated with improved response and decreased side effects. Although successful in many patients, this alternative route has several significant drawbacks, which include high initial cost, the need for specialized maintenance and possible mechanical complications, and the risk of bacterial contamination when the pump is accessed to refill or alter the delivered solution. There has been a constant search for methods which are more successful and associated with fewer side effects than our current systems. One approach under investigation has been the use of adrenal medullary allograft placed within the subarachnoid space.

The authors of this study report on a longitudinal survey which reviewed the effects of human chromaffin cell graft transplantation into 15 patients for intractable cancer pain after failure of systemic opioids due to the persistence of undesirable side effects. Prior to allograft transplantation, all patients required chronic intrathecal administration of morphine due to persistence of irreversible side effects after systemic opioids. The systemic opioids consisted primarily of oral morphine in a sustained release preparation and/or transdermal fentanyl. In these patients, pain was well controlled by delivery of intrathecal morphine with average pain scores between 0 and 2. Individual daily intrathecal morphine doses varied considerably and ranged from 1 to 45 mg per 24 hours. In the course of their study, a total of 20 allografts were carried out in 15 patients. Five patients received a second graft between the second and fifth month. This was performed either because of incomplete initial results or because it was thought that insufficient tissue had been grafted during the first intervention. This was documented by demonstration that the concentration of Met-enkephalin had not increased significantly compared to baseline. Patients were followed up from 15-370 days with a mean of 4.5 months. The main evaluation criteria of analgesic activity of the chromaffin cell allograft was the commentary requirement of analgesics and, in particular, the consumption of intrathecal morphine required to maintain effective pain control until the end stage of the disease.

Out of the 12 patients who received enhanced analgesia with long-term follow-up, five no longer required intrathecal morphine (with prolonged interruption of systemic opioids as well), two durably decreased intrathecal morphine intake and five were stabilized until the end of their follow-up. The authors interpreted durable decline and stabilization as indicative of analgesic activity by comparison with the usual dose escalation observed during disease progression. In most cases, they were able to demonstrate a relationship between analgesic responses and CSF Met-enkephalin levels. They concluded that the results of this phase II open study demonstrate the feasibility and safety of this approach using chromaffin cell grafts for long-term relief of intractable cancer pain. They qualified their results by commenting that while analgesic efficacy was indicated by the reduction or stabilization in complementary opioid intake, these observations will need to be confirmed in a controlled trial in a larger series of patients.

The control of severe pain from cancer remains a challenge in some patients. Although effective methods of controlling pain with oral medications have been developed and are frequently successful, they are also associated with significant side effects. More advanced methods, including neurolytic blocks or placement of intraspinal catheters either epidurally or intrathecally, may be associated with problems related to technical insertion of the catheter or pump device and the potential for infection or side effects related to the medication or procedure. The development of a cellular delivery mechanism that minimizes the risk of infection or mechanical equipment failure and is capable of delivering analgesic compounds with no appreciable side effects is an exciting prospect for future control of cancer pain. The development of human chromaffin cell grafts for control of pain has been and continues to be an exciting area of development within the field of pain medicine. These researchers and their techniques bear careful watching as they develop a valuable tool in the quest to treat pain in an improved fashion in the years to come.