Randomized Clinical Trial of an Implantable Drug Delivery System Compared With Comprehensive Medical Management for Refractory Cancer Pain: Impact on Pain, Drug-Related Toxicity, and Survival

Smith, Thomas J.; Staats, Peter S.; Deer, Timothy R.; Stearns, Lisa; Rauck, Richard; Boortz-Marx, Richard L.; Buchser, Eric; Català, E.; Bryce, David A.; Coyne, Patrick; Pool, George E.

doi:10.1200/jco.2002.02.118

Cited by 620 publications

(404 citation statements)

References 27 publications

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“…As analgesia after a single IT opioid administration lasts only a few hours, prolonged pain control requires the implantation of a pump and a permanent IT catheter. Although this approach has been shown to provide superior pain control in a randomized controlled clinical trial, 55 the method has not been adopted outside of few specialized medical centers fielding multi-specialty teams consisting of anesthesiologists, neurosurgeons and oncologists, who are able to service the implanted hardware and investigate acute complications, which might be related to the catheter.…”

Section: Pharmacological Rationale For Gene Therapy Targeting the Drgmentioning

confidence: 99%

AAV for pain: steps towards clinical translation

Beutler

Reinhardt

2009

Gene Ther

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Recombinant adeno-associated virus (rAAV) vectors consisting of self-complementary genomes and packaged in certain capsids can target primary sensory neurons efficiently and can control neuropathic pain long term by expressing opioid or non-opioid analgesic genes. This review examines the therapeutic potential of the approach in five sections: Pain control in oncology (including a discussion of cancer centers as translational pain research environment); vector biology; safety considerations and immunological lessons learned from rAAV clinical trials of other disorders; development of intrathecal rAAV therapy in rodent models of pain; and preclinical steps towards clinical translation of rAAV for pain. In the field of analgesic drug development, clinical validation of new approaches identified in rodents is currently a critical limiting step. Small-molecule therapeutics suitable as conventional drugs to probe novel targets in clinical trials are often unavailable. In this context, gene therapy could fill an important gap in the drug development process facilitating first-into-human trials of untested targeted treatments, each instantiated as a therapeutic gene.

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Section: Pharmacological Rationale For Gene Therapy Targeting the Drgmentioning

confidence: 99%

AAV for pain: steps towards clinical translation

Beutler

Reinhardt

2009

Gene Ther

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“…One RCT reported a non-significant trend for shorter survival in patients treated with oral opioids compared with intrathecal opioids for pain control (6 month survival 37% vs. 54%; p=0·06) [66]. Although the intrathecal group had a larger OME dose than the medically managed group, systemically the opioid concentration would be orders of magnitude less.…”

Section: Effect Of Opioids On Survivalmentioning

confidence: 99%

“…There were 3 RCTs, 3 prospective studies and 1 retrospective study (Table 1). These studies tended to be multicentre (Table 1) [18,29,65,66]. The mean sample size was 485 patients.…”

Section: Long Term Studies: Study Characteristicsmentioning

confidence: 99%

Is regular systemic opioid analgesia associated with shorter survival in adult patients with cancer? A systematic literature review

Boland

Ziegler

Boland

et al. 2015

Pain

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Opioids are important in the management of pain in patients with cancer. Clinicians and patients are sometimes concerned about the effect of opioids on survival, which might decrease opioid prescription, compliance and symptom control. We wanted to determine whether opioid analgesia was associated with shorter survival in adult patients with cancer. We systematically searched for studies that assessed the effect of regular systemic opioid analgesia on survival. We identified 526 unique records, with 20 articles meeting inclusion criteria. Thirteen end-of-life studies, including 11 very low quality retrospective studies, did not find a consistent association between opioid analgesic treatment and survival, this evidence comes from low quality studies, so should be interpreted with caution. Seven longer-term studies, including 3 randomised controlled trials and 2 prospective studies were included. Six of these studies indicated that opioids were likely to be associated with a shorter survival. None of these studies were powered to assess the effect of opioids on survival as a primary endpoint. In view of this, no definitive conclusions can be made as to whether opioids affect survival in cancer patients. These data suggest that while opioid analgesia does not affect survival at the end of life, in the context of longer-term treatment, higher quality studies, with survival as a primary endpoint, are needed to confirm an independent association between opioid analgesia and shorter survival. An important limitation of research in this field is that the relationship between greater analgesic requirements and shorter survival may be mediated by painful progressive cancer.

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“…The authors identified three randomized controlled trials comparing intraspinal with systemic analgesia [2][3][4]. The first study by Vanino et al found no statistically significant difference in pain [2]; the second study by Smith et al revealed a borderline statistical significance of questionable clinical value [3], while the third council study revealed no difference in pain control between epidural and subcutaneous administration of morphine [4]. The methodologic quality of the three included studies needs to be highlighted.…”

mentioning

confidence: 99%

“…Two studies reported no sample size calculations, and both appeared to be under-powered [2,4]. Two were open-label studies [2,3] which could significantly affect how pain and side effects were assessed. Finally, all were supported by pharmaceutical companies.…”

mentioning

confidence: 99%