2012 Is ‘Banner Year’ for Research on Symptom Management


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It’s important to think about what [palliative care] characteristics you can provide or integrate into your care for your patients to improve upon outcomes.

— Debra L. Barton, RN, PhD

The year 2012 was “a banner year for symptom management,” according to Debra L. Barton, RN, PhD, of the Mayo Clinic, Rochester, Minnesota, who presented data on patient and survivor care at the Best of ASCO San Diego meeting. “I have been doing symptom management for about 20 years, and it seems like way too often we have way too many negative studies, and I’d be saying, here is a litany of things that don’t help patients,” she said. “However, this year, we actually have positive studies.” 

Agents for Managing Peripheral Neuropathy

The Cancer and Leukemia Group B (CALGB) 170601 phase III trial tested duloxetine (Cymbalta)—an antidepressant that blocks serotonin and norepinephrine reuptake—for treatment of painful chemotherapy-induced peripheral neuropathy.1 In a randomized, crossover design, 220 patients with painful neuropathy from paclitaxel or oxaliplatin were given duloxetine with the dose gradually titrated upward or placebo for 5 weeks, and then switched to the alternative treatment.

Mean scores were lower with duloxetine vs placebo for both pain (P = .003; effect size, 0.513) and its interference with daily activities (P = .015). Patients were more likely to have any pain reduction and at least a 30% reduction on duloxetine. Rates of adverse events were generally similar with the drug and placebo, although dropouts were more common with the former.

Duloxetine is “the very first pharmacologic agent found effective for reducing pain from peripheral neuropathy,” Dr. Barton noted. “Is this practice-changing? You betcha!” she commented.

“It is important to titrate dose up for tolerability, beginning at 30 mg and then going up to 60 mg,” she recommended. Two weeks at that target dose should be sufficient to tell if the drug is working.

The randomized Southwest Oncology Group (SWOG) S0715 trial tested use of acetyl-L-carnitine—a derivative of endogenous L-carnitine marketed as a weight loss product—for the prevention of taxane-induced neuropathy during adjuvant breast cancer therapy in 409 patients.2 Relative to the placebo group, acetyl-L-carnitine recipients were more likely to have a worsening of neurologic symptoms from baseline at 24 weeks (38% vs 28%, HR = 1.50, P = .05) and to develop grade 3/4 peripheral neuropathy (4% vs < 1%).

“It’s very important to inform patients to avoid acetyl carnitine for prevention of chemotherapy-induced neuropathy,” Dr. Barton contended. “Granted, you could say you can’t necessarily apply these results to other neurotoxic agents. But given that in every single outcome, neuropathy got worse, I sure wouldn’t encourage patients to take this for non–paclitaxel-induced neuropathy.”

Ginseng for Cancer-related Fatigue

The North Central Cancer Treatment Group (NCCTG) phase III N07C2 trial assessed use of ginseng, which has anti-inflammatory and cortisol-regulating properties, to improve cancer-related fatigue in 339 oncology patients.3 Patients were randomized to Wisconsin ginseng (Panax quinquefolius) in ground root form or placebo for 8 weeks.

The ginseng group had a greater change in the 100-point Multidimensional Fatigue Symptom Inventory from baseline at 4 weeks (14.4 vs 8.2 points, P = .07) and 8 weeks (20.0 vs 10.3, P = .003). Rates of toxicity due to any cause did not differ. The fatigue-reducing benefit of ginseng was greater among the 49% of patients still in active cancer treatment.

“Admittedly, the impact on fatigue was not large,” Dr. Barton commented. “Since ginseng is not an FDA-regulated product, there is a lot of variability in over-the-counter products, and patients need to be counseled about this,” she said.

“I do think it is reasonable to try ginseng for fatigue, particularly since there are no other pharmacologic agents that are helpful for this,” she continued. “It’s important not to use extracts, because extracts can be made with methanol, which actually causes characteristics of the ginseng to be estrogenic.”

Aromatase Inhibitor–related Musculoskeletal Events

The randomized VITAL trial assessed use of vitamin D3 to prevent worsening of musculoskeletal symptoms in 160 women with breast cancer starting adjuvant therapy with the aromatase inhibitor letrozole who had suboptimal levels of 25-hydroxyvitamin D (≤ 40 ng/mL).4 They were assigned to vitamin D3 at 30,000 IU weekly or placebo weekly, each added to the recommended dietary allowances of calcium and vitamin D.

Patients in the vitamin D group had a lower incidence of any musculoskeletal event defined as worsening pain, worsening disability, and/or discontinuation of letrozole. The benefit differed when worsening pain was assessed with a simple descriptive pain scale (37% vs 51%, P = .069) or with the Brief Pain Inventory (38% vs 61%, P = .008).

“I think their biggest limitation was their primary endpoint. It’s really hard for me to get my arms around what benefit or lack of benefit women receive in either of those two groups, especially when you consider those three criteria—they are very different in my mind,” Dr. Barton commented. “It’s also a little concerning to me that the significance of the primary endpoint changed according to what measure was used,” she added.

“Is this practice-changing? Not quite yet,” she said (see sidebar on page 111, “Is Vitamin D Supplementation Ready for Prime Time?”). “The main reason why it wouldn’t universally be practice-changing is because of that outcome weakness.”

Early Palliative Care Improves Outcomes

In a cluster-randomized trial at a tertiary center, investigators assigned oncology clinics to use standard care (patients seen by palliative care team on request with follow-up as required) or early palliative care (patients seen by palliative care team within a month with monthly follow-up) for adults with metastatic cancer.5 Analyses were based on 233 patients receiving standard care and 228 patients in the intervention group, most of whom were getting active chemotherapy.

Relative to patients in the standard care group, patients in the palliative care group had more favorable mean changes at 4 months in scores for quality of life (P = .007), symptom control (P = .05), and satisfaction with care (P < .001).

“It’s important that the extra clinic visits from the palliative care team were not overly burdensome. A vast majority of patients got four palliative care visits or less, so we aren’t talking about a whole bunch of extra work,” Dr. Barton maintained.

This study “further supports the mounting data out there on the benefits of early palliative care,” she contended. “So if your institution has a palliative care team, refer. If your institution is thinking about creating a palliative care team, help. And if you don’t have a palliative care team or palliative care providers, it’s important to think about what characteristics you can provide or integrate into your care for your patients to improve upon outcomes such as we have seen in these early palliative care studies,” she recommended, pointing to ASCO’s provisional clinical opinion endorsing early palliative care and outlining its key elements.6

Comprehensive Centers and Racial Disparities

A cross-sectional study in Los Angeles compared outcomes between adolescents and young adults treated at three National Cancer Institute–designated Comprehensive Cancer Centers (NCICCCs) with those of their counterparts treated at all other centers.7 Among the 10,602 patients studied, just 9% received care at an NCICCC. The 10-year rate of overall survival was better for patients treated in these centers than for their peers treated at others (83% vs 81%, P = .02). “Although it’s statistically significant because there were more than 10,000 people, it’s a difference of only 2% to 3%,” Dr. Barton noted.

Compared with white youth, black and Hispanic youth fared significantly more poorly at non-NCICCCs, but not at NCICCCs. Race/ethnicity, socioeconomic status, and health insurance status all influenced access to care at NCICCCs (P < .001 for each), with higher proportions of white, better-off, and privately insured youth obtaining care in these centers.

“The investigators say future directions [in research] are to understand the barriers to care at a Comprehensive Cancer Center,” Dr. Barton said. “I actually would like to know what characteristics account for better survival at Comprehensive Cancer Centers so that we can spread them around to all cancer centers, so that everybody everywhere has good outcomes.” ■

Disclosure: Dr. Barton reported no potential conflicts of interest.

References

1. Lavoie Smith EM, Pang H, Cirrincione C, et al: CALGB 170601: A phase III double blind trial of duloxetine to treat painful chemotherapy-induced peripheral neuropathy (CIPN). 2012 ASCO Annual Meeting. Abstract CRA9013. Presented June 5, 2012.

2. Hershman DL, Unger JM, Crew KD, et al: SWOG S0715: Randomized placebo-controlled trial of acetyl-L-carnitine for the prevention of taxane-induced neuropathy during adjuvant breast cancer therapy. 2012 ASCO Annual Meeting. Abstract 9018. Presented June 4, 2012.

3. Barton DL, Liu H, Dakhil SR, et al: Phase III evaluation of American ginseng (Panax quinquefolius) to improve cancer-related fatigue: NCCTG trial N07C2. 2012 ASCO Annual Meeting. Abstract 9001. Presented June 4, 2012.

4. Khan QJ, Kimler BF, Reddy PS, et al: Randomized trial of vitamin D3 to prevent worsening of musculoskeletal symptoms and fatigue in women with breast cancer starting adjuvant letrozole: The VITAL trial. 2012 ASCO Annual Meeting. Abstract 9000. Presented June 4, 2012.

5. Zimmermann C, Swami N, Rodin G, et al: Cluster-randomized trial of early palliative care for patients with metastatic cancer. 2012 ASCO Annual Meeting. Abstract 9003. Presented June 4, 2012.

6. Smith TJ, Temin S, Alesi ER, et al: American Society of Clinical Oncology provisional clinical opinion: The integration of palliative care into standard oncology care. J Clin Oncol 30:880-887, 2012.

7. Wolfson JA, Sun C-L, Kim H, et al: Evaluation of the effect of care at NCI comprehensive cancer centers (NCICCCs) on disparities in outcome within adolescents and young adults (AYAs) with cancer. 2012 ASCO Annual Meeting. Abstract 9512. Presented June 4, 2012.


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SIDEBAR: Is Vitamin D Supplementation Ready for Prime Time?

The VITAL study generated a host of questions about vitamin D among ASCO Annual Meeting attendees, including whether the study’s findings are ready for clinical application, according to Debra L. Barton, RN, PhD, of the Mayo Clinic, Rochester, Minnesota, speaking at the Best of ASCO San Diego...


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