Exploratory Study on the Use of Pregabalin for the Treatment of Taxol Related Arthralgia-Myalgia
试验速览
- 阶段
- 2 期
- 入组人数
- 38
- 试验地点
- 1
- 主要终点
- Integrated Numeric Pain Scores and Rescue Analgesic Medication Requirement as calculated by the method proposed by Silverman et al (Silverman, O'Connor et al. 1993).
研究概览
简要总结
Paclitaxel is chemotherapeutic agent used in many of the most common anti-cancer regimens. Its use is frequently associated with moderate to severe muscle and joint pain that may persist for several days after the treatment. This side effect, known as "Arthralgia-Myalgia Syndrome, has a significant impact on the quality of life and functional abilities of those receiving the treatment, and is not alleviated by many of the interventions attempted for that purpose.
Sporadic reports suggest that a drug called gabapentin may be effective in the management of this adverse effect. Observations from our practice indicate that pregabalin, which possesses similar biological activity to that of gabapentin, may also be useful in preventing and treating paclitaxel associated myalgia - arthralgia.
The current study represents an initial evaluation of the hypothesis that pregabalin may be beneficial in the management of the symptoms due to the "Arthralgia-Myalgia Syndrome". The investigation will be carried out in the format of a small scale, randomized, placebo controlled trial with patients receiving paclitaxel in the course of standard treatment for breast cancer.
详细描述
Taxane Related Arthralgia-Myalgia Syndrome:
Paclitaxel and docetaxel are the major representatives of the drug class of taxanes, agents commonly used in the treatment of a variety of solid tumors. They interfere with the mitotic process of dividing cells by stabilizing the microtubules and are the mainstay of treatment in lung, breast, and ovarian cancer, among others. The adverse side effects associated with taxane treatment frequently impair the quality of life of cancer patients and occasionally impose discontinuation of the oncological treatment of choice (Forsyth, Balmaceda et al. 1997; Saibil, Fitzgerald et al. 2010).
The phenomenon of diffuse pain involving joints and muscles in the wake of treatment with taxanes commonly referred to as Taxane related Arthralgia-Myalgia Syndrome (from here on noted as TAMS) is well known and documented (Rowinsky, Chaudhry et al. 1993). It is common, as apparent from a recent retrospective study of patients treated with regimens used for breast cancer which revealed an 80% incidence of taxane related pain (Saibil, Fitzgerald et al. 2010).
The pain may be localized, regional or diffuse, most commonly in the back, hips, shoulders, thighs, legs and feet (Loprinzi, Maddocks-Christianson et al. 2007). It is usually depicted as arthralgia-myalgia due to the difficulty to associate it clearly with either the joints or the muscles (Loprinzi, Maddocks-Christianson et al. 2007). The nature of the sensation is described as aching, deep pain, often with associated radiating, shooting, stabbing, pulsating elements (Loprinzi, Maddocks-Christianson et al. 2007). The sensation is of unique quality previously unencountered by those experiencing it, the description of which is not compatible with established reports of neuropathic pain.
The syndrome may be of incapacitating intensity, capable of imposing days of bed restriction on those suffering from it. This burden is often extended to significant others who have to remain and care for the daily needs of those handicapped by the pain. Attempts of treatment with steroids, non-steroid anti-inflammatory drugs and opioid analgesics frequently fail to produce satisfactory results (Garrison, McCune et al. 2003).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •Ongoing treatment with pregabalin or gabapentin.
- •Known restricting adverse events related to treatment with pregabalin or gabapentin.
- •Renal failure with GFR less than 30ml/min.
- •Participation in clinical trial 3 weeks or less prior to screening.
- •Confounding myalgia and / or arthralgia unrelated to chemotherapy.
- •Medical condition compromising the likelihood of completing the trial.
研究组 & 干预措施
Pregabalin
Includes 19 out of 38 subjects reporting athralgia-myalgia in the wake of paclitaxel infusion in the course of breast cancer treatment.
Pregabalin started on the evening before receiving infusion of paclitaxel and 5 day thereafter. Initial dosing of 75mg twice daily (morning + evening). Option for dose increase with additional 75mg in case of inadequate pain control. A minimal interval of 2 hours is required between doses.
In case of poorly tolerated side effects a reduction to 50mg doses is available.
Access to additional analgesic interventions is open as required for patient wellbeing.
干预措施: Pregabalin (Drug)
Placebo
Includes 19 out of 38 subjects reporting athralgia-myalgia in the wake of paclitaxel infusion in the course of breast cancer treatment.
Placebo externally identical to the pregabalin 75mg capsules will be started on the evening before receiving infusion of paclitaxel and 5 day thereafter. Initial dosing of 1 capsule twice daily (morning + evening). Option for dose increase with additional capsule in case of inadequate pain control. A minimal interval of 2 hours is required between doses.
In case of poorly tolerated side effects a reduction to capsules with the appearance of 50mg pregabalin capsules is available.
Access to additional analgesic interventions is open as required for patient wellbeing.
干预措施: Placebo (Drug)
结局指标
主要结局
Integrated Numeric Pain Scores and Rescue Analgesic Medication Requirement as calculated by the method proposed by Silverman et al (Silverman, O'Connor et al. 1993).
时间窗: 16 months from study initiation
Modern pain research acknowledges the subjective and complex nature of pain that complicates its assessment. Furthermore, ethical imperatives place constraints on the comparative control to serve the in evaluation of a novel analgesic intervention (Silverman, O'Connor et al. 1993). One of the solutions to this issue, using normalized ordinal evaluations of pain and analgesic drug consumption around a central value in a manner that also accounts for changes in analgesic drug requirements (Silverman, O'Connor et al. 1993) will serve for direct assessment of the study hypothesis.
次要结局
- The additional number of hours spent in horizontal position (∆HHP**)(8 days after receiving cycle of paclitaxel)
- FACT-taxane score(On day of recruitment to active phase + one week after 4th cycle of paclitaxel since recruitment to active phase.)
- Numeric Pain Score (NPS)(8 days after receiving cycle of paclitaxel)