Omega-3 Fatty Acid in Treating Pain in Patients With Breast or Ovarian Cancer Receiving Paclitaxel
| Status: | Active, not recruiting |
|---|---|
| Conditions: | Breast Cancer, Ovarian Cancer, Cancer, Chronic Pain |
| Therapuetic Areas: | Musculoskeletal, Oncology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 2/2/2019 |
| Start Date: | February 2013 |
| End Date: | June 2020 |
A Pilot Randomized, Placebo Controlled, Double Blind Study of Omega-3 Fatty Acids to Prevent Paclitaxel Associated Acute Pain Syndrome
Paclitaxel, a widely used chemotherapeutic agent, is associated with several well-known side
effects including neuropathy (weakness, numbness and pain) and generalized body aches. The
latter has recently been described as paclitaxel-associated acute pain syndrome (P-APS) and
often occurs in the first three to four days after administration. It affects about 58-90% of
patients. Currently, the mechanism of P-APS is unknown, and there is no standard of care to
treat it. However, an intervention with both anti-inflammatory as well as neuroprotective
properties would be an ideal candidate for testing in the prevention of P-APS and subsequent
development of peripheral neuropathy. Previous studies have suggested that omega-3 fatty
acids may act as neuroprotective agents, and there are no currently documented safety
concerns with their combined use with paclitaxel.
Therefore, this randomized pilot clinical trial will determine whether omega-3 fatty acids
can treat pain in patients with breast or ovarian cancer receiving paclitaxel.
effects including neuropathy (weakness, numbness and pain) and generalized body aches. The
latter has recently been described as paclitaxel-associated acute pain syndrome (P-APS) and
often occurs in the first three to four days after administration. It affects about 58-90% of
patients. Currently, the mechanism of P-APS is unknown, and there is no standard of care to
treat it. However, an intervention with both anti-inflammatory as well as neuroprotective
properties would be an ideal candidate for testing in the prevention of P-APS and subsequent
development of peripheral neuropathy. Previous studies have suggested that omega-3 fatty
acids may act as neuroprotective agents, and there are no currently documented safety
concerns with their combined use with paclitaxel.
Therefore, this randomized pilot clinical trial will determine whether omega-3 fatty acids
can treat pain in patients with breast or ovarian cancer receiving paclitaxel.
One mechanism proposed for P-APS is an early inflammatory process characterized by macrophage
activation in both the dorsal root ganglia and peripheral nerve occurring shortly after
paclitaxel therapy. Morphologic alterations in DRG satellite cells have been noted and
upregulation of proinflammatory cytokines have been hypothesized as early events in the
development of neuropathy. Therefore, it is possible that paclitaxel-induced neuropathic pain
may be mediated by pro-inflammatory cytokines. If P-APS and chronic neuropathy are indeed
part of a continuum, the inflammatory pathway would be a reasonable target for therapy. While
the mechanism of how paclitaxel leads to the development of neuropathy is still not
understood, it has been hypothesized that its microtubule-stabilizing effects disrupt axonal
transport. Intervention with an agent that is both anti-inflammatory as well as
neuroprotective is therefore worth exploring.
Long chain omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA),
are common dietary supplements. They have well established anti-inflammatory properties which
serve as the basis for their use in therapeutic trials in inflammatory conditions. Omega -3
fatty acids consumption can attenuate the production of pro-inflammatory metabolites. In
addition, it can generate local mediators that facilitate resolution of inflammation. Thus,
if P-APS is indeed mediated by inflammation, the anti-inflammatory activity of omega 3 fatty
acids may be one mechanism to prevent P-APS. Additionally, given its well established safety
profile, it may be an attractive alternative to NSAIDS.
A dose of at least 2.7 g/day of EPA and DHA have been reported to have analgesic effects in
inflammatory conditions. The dose of 4 g/day is an FDA-approved dose of omega 3 fatty acids
(Lovaza) for the treatment of hypertriglyceridemia and has a well-documented toxicity
profile. On the basis of this, a dose of 4 g/day was selected for this study. Lovaza
(omega-3-acid ethyl esters) capsules will be used. Each 1-gram capsule contains approximately
465 mg EPA and 375 mg DHA.
activation in both the dorsal root ganglia and peripheral nerve occurring shortly after
paclitaxel therapy. Morphologic alterations in DRG satellite cells have been noted and
upregulation of proinflammatory cytokines have been hypothesized as early events in the
development of neuropathy. Therefore, it is possible that paclitaxel-induced neuropathic pain
may be mediated by pro-inflammatory cytokines. If P-APS and chronic neuropathy are indeed
part of a continuum, the inflammatory pathway would be a reasonable target for therapy. While
the mechanism of how paclitaxel leads to the development of neuropathy is still not
understood, it has been hypothesized that its microtubule-stabilizing effects disrupt axonal
transport. Intervention with an agent that is both anti-inflammatory as well as
neuroprotective is therefore worth exploring.
Long chain omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA),
are common dietary supplements. They have well established anti-inflammatory properties which
serve as the basis for their use in therapeutic trials in inflammatory conditions. Omega -3
fatty acids consumption can attenuate the production of pro-inflammatory metabolites. In
addition, it can generate local mediators that facilitate resolution of inflammation. Thus,
if P-APS is indeed mediated by inflammation, the anti-inflammatory activity of omega 3 fatty
acids may be one mechanism to prevent P-APS. Additionally, given its well established safety
profile, it may be an attractive alternative to NSAIDS.
A dose of at least 2.7 g/day of EPA and DHA have been reported to have analgesic effects in
inflammatory conditions. The dose of 4 g/day is an FDA-approved dose of omega 3 fatty acids
(Lovaza) for the treatment of hypertriglyceridemia and has a well-documented toxicity
profile. On the basis of this, a dose of 4 g/day was selected for this study. Lovaza
(omega-3-acid ethyl esters) capsules will be used. Each 1-gram capsule contains approximately
465 mg EPA and 375 mg DHA.
Inclusion Criteria:
- Patients have a diagnosis of breast cancer or ovarian cancer
- Patients are scheduled to receive weekly paclitaxel at 70-90 mg/m^2 for a minimum of 2
months; 3 out of 4 weeks is allowed
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1 or 2
- Patients must not have taken omega-3-fatty acid supplements within the past 1 month
prior to registration and must agree to refrain from use of omega- 3 fatty acid
supplements from sources outside the study
- Patients must not be on nonsteroidal anti-inflammatory drugs (NSAIDS) or aspirin for
at least 1 week prior to registration; NSAIDS or aspirin are allowed after enrollment
- Patients must not have received any other analgesics (opiates and tramadol) 1 week
prior to registration; analgesics (opiates and tramadol) are allowed after enrollment
- Patients must have the ability to complete questionnaires by themselves or with
assistance
- Patients must not be on anticoagulation medication (heparin/ warfarin) within 28 days
prior to registration, because of increased risk of bleeding
- Concurrent treatment with carboplatin +/- bevacizumab is allowed
- Concurrent treatment with human epidermal growth factor receptor (Her2 neu) targeted
therapy is allowed
Exclusion Criteria:
- Known allergy to omega 3 fatty acids, fish or shellfish
- Pre-existing diagnosis of peripheral neuropathy
- Diagnosis of fibromyalgia
- Concurrent planned neutrophil colony stimulating factor therapy
- Prior exposure to paclitaxel within the last 6 months
We found this trial at
2
sites
Albuquerque, New Mexico 87131
Principal Investigator: Zoneddy R. Dayao
Phone: 505-925-5490
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