Despite our study's limitations, results suggest that long-term IDDS for refractory malignant pain due to pancreatic cancer was both efficacious and safe in pancreatic cancer pain. We have demonstrated, in the largest series of IDDS for pancreatic cancer pain reported yet, a clinically and statistically significant pain reduction in patients receiving IDDS.
Background: Ziconotide is a new analgesic agent administered intrathecally. It is challenging
to use and can induce several and sometimes serious adverse events. A low initial dosage
followed by slow titration may reduce serious adverse events.
Objective: To determine whether a low starting dosage of ziconotide, followed by slow
titration, decreases the incidence of major adverse events associated with ziconotide when
used for intractable cancer pain.
Study Design: Observational cohort study.
Setting: Three French cancer centers.
Methods: Patients with incurable cancer causing chronic pain rated above 6/10 on
a numerical scale while receiving high-dose opioid therapy (more than 200 mg/d of oral
morphine equivalent) and/or exhibiting severe opioid-related adverse events received
intrathecal infusions of ziconotide combined with morphine, ropivacaine, and clonidine.
Results: Seventy-seven patients were included. Adverse events were recorded in 57%
of them; moderate adverse events occurred in 51%. Adverse events required treatment
discontinuation in 7 (9%) including 5 (6%) for whom a causal role for ziconotide was highly
likely; among them 4 (5%) were serious. All patients experienced a significant and lasting
decrease in pain intensity (by 48%) in response to intrathecal analgesic therapy that included
ziconotide.
Limitations: Limitations include the nonrandomized, observational nature of the study.
Determining the relative contributions of each drug to adverse events was difficult, and some
of the adverse events manifested as clinical symptoms of a subjective nature.
Conclusions: The rates of minor and moderate adverse events were consistent with
previous reports. However, the rate of serious adverse events was substantially lower. Our
study confirms the efficacy of intrathecal analgesia with ziconotide for relieving refractory
cancer pain. These results indicate that multimodal intrathecal analgesia in patients with
cancer pain should include ziconotide from the outset in order to provide time for subsequent
slow titration.
Key words: Ziconotide, adverse events, intrathecal therapy, cancer pain, morphine,
ropivacaine, clonidine.
Objective
Intrathecal (IT) drug delivery has shown its efficiency in treating refractory cancer pain, but switching opioids from the systemic to the intrathecal route is a challenging phase. Moreover, associations are widely used and recommended. Few data deal with the initial dosage of each drug. Analyzing conversion factors and initial dosages used in intrathecal therapy seems essential to decreasing the length of titration and to delivering quick pain relief to patients.
Methods
We retrospectively analyzed data from consecutive adult patients implanted with an intrathecal device for cancer pain and treated at the Institut de Cancérologie de l’Ouest, in Angers, France, for four years. The main goal was to identify factors associated with early pain relief after intrathecal drug delivery system (IDDS) implantation.
Results
Of the 220 IDDS-treated patients, 70 (32%) experienced early pain relief (EaPR) and 150 (68%) delayed pain relief (DePR). Performance Status stage and initial IT ropivacaine:IT morphine ratio were the variables independently associated with EaPR. The best IT ropivacaine:IT morphine ratio to predict EaPR was 5:1, with a 73% (95% confidence interval [CI] = 64.8% to 79.6%) sensitivity and a 67.1% (95% CI = 54.9% to 77.9%) specificity. EaPR subjects experienced better pain relief (–84% vs –60% from baseline pain score, P < 0.0001), shorter length of hospitalization (7 vs 10 days, P < 0.0001), and longer survival (155 vs 82 days, P = 0.004).
Conclusions
Local anesthetic:morphine ratio should be considered when starting IDDS treatment. EaPR during the IT analgesia titration phase was associated with better pain relief and outcomes in patients with refractory cancer-related pain.
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