An implantable drug delivery system (IDDS) for refractory cancer pain provides sustained pain control, less drug-related toxicity, and possibly better survival compared with comprehensive medical management (CMM)

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

doi:10.1093/annonc/mdi156

Cited by 166 publications

(109 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In this latter study, Smith et al showed that ITA led to improved cancer pain control and less drug toxicity after four weeks [228]. (Subsequently, this RCT rendered two additional publications [226,227]). Hence, according to the standards of evidence-based medicine, there is a paucity of high-quality studies.…”

Section: Intrathecal Analgesia In Cancer Painmentioning

confidence: 99%

The Cerebrospinal Fluid in Severe Pain Conditions : Clinical, Pharmacological and Proteomic Aspects

Bäckryd¹

2015

View full text Add to dashboard Cite

The treatment of both cancer pain and non-cancer chronic pain is still suboptimal. The overall aim of this PhD thesis was to conduct translational pain research at the interface between clinical pain medicine and the field of human proteomics, using the practice of intrathecal analgesia at our institution as a starting point. Hence, the cerebrospinal fluid (CSF) is at the centre of the present dissertation, both as a target for infusing analgesics (Papers I and II – clinical and pharmacological aspects) and as an important biofluid for human biomarker studies (Papers III and IV – proteomic aspects). In Paper I, 28 cases of intrathecal analgesia in cancer patients were prospectively followed. Movement-evoked breakthrough pain remained a major clinical problem throughout the study month despite otherwise successful intrathecal analgesia (defined as good control of spontaneous resting pain paralleled by a marked decrease of concomitant systemic opioid doses). This study therefore illustrates the importance of considering not only spontaneous resting pain but also movement-evoked breakthrough pain. In Paper II, an expert-based algorithm for trialing the intrathecal analgesic ziconotide by bolus injections was evaluated in an open-label study of 23 patients with chronic neuropathic pain. We found few responders (13%) according to the strict criteria of the algorithm, but ziconotide bolus injection trialing seems feasible. The predictive power of ziconotide bolus trialing remains unclear, and the pharmacological profile of ziconotide (with very slow tissue penetration due to high hydrophilicity) calls the rationale for ziconotide bolus trialing into question. In Paper III, we found low levels of beta-endorphin in the CSF of chronic neuropathic pain patients (n=15) compared to healthy controls (n=19). We speculate that this might indicate dysfunctional top-down control of nociception. Substance P levels in the CSF did not differ by univariate statistics. In Paper IV, the CSF proteome of 11 patients with chronic neuropathic pain and 11 healthy controls was exploratively studied, combining gel-based proteomics with multivariate data analysis. After eliminating four proteins associated with age, 32 proteins were found to highly discriminate between groups. Among these, the seven proteins having the highest discriminatory power between patients and controls were: one isoform of angiotensinogen, two isoforms of alpha-1-antitrypsin, three isoforms of haptoglobin, and one isoform of pigment epithelium-derived factor. In conclusion, this PhD thesis demonstrates the fruitfulness of studying the CSF, both as a target for infusing analgesics and as a potential mirror of the neurobiological processes involved in pathological pain conditions. The thesis points to the need for more research into the mechanisms of different pain conditions, in order to hopefully achieve the vision of mechanism-based pain diagnoses

show abstract

Section: Intrathecal Analgesia In Cancer Painmentioning

confidence: 99%

The Cerebrospinal Fluid in Severe Pain Conditions : Clinical, Pharmacological and Proteomic Aspects

Bäckryd¹

2015

View full text Add to dashboard Cite

show abstract

“…Utilizing multiple medications in conjunction may reduce pain at decreased doses of the medications and decrease side effects of high doses of any one medication. The reduction in opioid side-effects in patients in a randomized control trial where patients were assigned to either medical management versus implantable drug delivery systems were reported to be as high as 50% [10]. In addition to better pain control and less side effects, intrathecal therapy may even lead to better survival, compared with comprehensive medical management [10].…”

Section: Editorialmentioning

confidence: 99%

Untitled

2016

BAOJPM

View full text Add to dashboard Cite

“…Although the intrathecal group had a larger OME dose than the medically managed group, systemically the opioid concentration would be orders of magnitude less. Pain control was better and less opioid toxicity was reported in the intrathecal group which might have contributed to the potential survival benefit [66,68]. Another RCT evaluated opioid use on endocrine function and survival (survival was not the primary outcome), despite the median OME being low (females 40mg and males 80 mg/d), survival was shorter (median 78 days) in opioid-using male patients compared with non-opioid-users (median 132 days; p=0·009) [29].…”

Section: Effect Of Opioids On Survivalmentioning

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

View full text Add to dashboard Cite

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.

show abstract

An implantable drug delivery system (IDDS) for refractory cancer pain provides sustained pain control, less drug-related toxicity, and possibly better survival compared with comprehensive medical management (CMM)

Abstract: IDDS improved clinical success, reduced pain scores, relieved most toxicity of pain control drugs, and was associated with increased survival for the duration of this 6 month trial.

Cited by 166 publications

References 14 publications

The Cerebrospinal Fluid in Severe Pain Conditions : Clinical, Pharmacological and Proteomic Aspects

The Cerebrospinal Fluid in Severe Pain Conditions : Clinical, Pharmacological and Proteomic Aspects

Untitled

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

Contact Info

Product

Resources

About