Clinical Insights: January/February 2015
CE lesson worth 1.0 contact hours that are intended for advanced practice nurses, registered nurses, and other healthcare professionals who care for cancer patients.
STATEMENT OF NEED
The overall goal is to update the healthcare professional’s knowledge of cancer detection and prevention and to understand current and new research regarding state-of-the-art care for those with or at risk for cancer.
Intended for advanced practice nurses, registered nurses, and other healthcare professionals who care for cancer patients.
OVERALL EDUCATIONAL OBJECTIVES
Upon completion, participants should be able to:
- Describe new preventive options and treatments for cancer patients
- Identify options for individualizing the treatment for cancer patients
- Review new evidence to facilitate survivorship and supportive care for cancer patients
Dannemiller is approved by the California Board of Registered Nursing, Provider Number 4229, for 1.0 contact hour. CBRN credit is not accepted by the Michigan and Utah State licensing boards.
The planners and authors of this CE activity have disclosed no relevant financial relationships with any commercial companies pertaining to this activity.
METHOD OF PARTICIPATION
- Read the articles in this section in its entirety.
- Go to www.dannemiller.com/onn-jan-feb-2015
- Complete and submit the CE posttest and activity evaluation.
- Print your Certificate of Credit.
This activity is provided free of charge to participants.
Less Frequent Dosing of Pancreatic Cancer Regimen Effective, Less Toxic
Changing the administration schedule for gemcitabine plus nab-paclitaxel from weekly to every other week significantly reduced side effects without impacting efficacy as a frontline treatment for patients with metastatic pancreatic cancer, according to a retrospective study presented at the 2015 GI Cancers Symposium. Abstract 366
The less intense treatment schedule demonstrated a median overall survival (OS) of 11.1 months and a median progression-free survival (PFS) of 4.8 months.
“Shifting this treatment to every other week gives the immune system time to recover between chemotherapy sessions and results in less overall toxicity. It also means fewer visits to the infusion center to receive chemotherapy,” study author Tanios Bekaii-Saab, MD, GI oncology section chief at The Ohio State University Comprehensive Cancer Center (OSUCCC)—James, said in a statement.
The FDA’s approval of the combination regimen in September 2013 was based on results from the MPACT trial, which showed that weekly nabpaclitaxel combined with gemcitabine significantly improved both OS and PFS. In the study, the median OS was 8.5 months with nab-paclitaxel plus gemcitabine versus 6.7 months with gemcitabine alone. The median PFS was 5.5 months with the combination versus 3.7 months with gemcitabine alone.
The single-institution retrospective study looked at 69 patients with pancreatic cancer who received the gemcitabine and nab-paclitaxel regimen on days 1 and 15 of a 28-day treatment cycle.
Compared with the MPACT study, the rate of adverse events was considerably lower. The incidence of neurological toxicity was less than 2% with the adjusted regimen compared with 17% in the MPACT study. Severe low blood cell counts were seen in 10% of patients with the every other week dose versus 38% with the weekly schedule. Growth factor injections were required in 8% of patients in the database analysis compared with 26% in the MPACT study. Grade 3 or greater neutropenia, anemia, thrombocytopenia, fatigue, and diarrhea were markedly less with the less intense regimen.
Avoiding Surgery in Patients With Rectal Cancer
A “watch and wait” surveillance approach may allow certain patients with rectal cancer to achieve excellent outcomes without immediate surgery, according to a retrospective review of clinical data presented at the 2015 GI Cancers Symposium. Abstract 509
The review found that patients with stage I-III rectal cancer whose tumors completely disappeared after treatment had similar 4-year survival rates regardless of whether they had immediate rectal surgery or took a nonoperative management (NOM) approach.
The findings from this study build on prior evidence from research conducted in Brazil and the Netherlands and may impact treatment decisions going forward, says senior study author Philip Paty, MD, a surgical oncologist at Memorial Sloan Kettering Cancer Center (MSK). “We believe that our results will encourage more doctors to consider this watch and wait approach in patients with clinical complete response as an alternative to immediate rectal surgery, at least for some patients,” said Paty. “From my experience, most patients are willing to accept some risk to defer rectal surgery in hope of avoiding major surgery and preserving rectal function.”
The review analyzed 442 patients treated at MSK from 2006 to 2013. Rectal surgery was deferred in 73 of these patients who experienced a clinical complete response after radiation and chemotherapy. A comparison group was formed from 72 patients that underwent standard rectal surgery and experienced a pathologic complete response.
Among the 73 NOM patients, 54 (74%) experienced durable tumor regression and avoided rectal surgery, whereas 19 (26%) later underwent rectal surgery to treat tumor regrowth. However, this regrowth proved to be manageable and was successfully resected. Of the 19 NOM patients with tumor regrowth, two were salvaged successfully, with local excision resulting in rectal preservation; the remaining 17 patients underwent rectal resections.
The 4-year overall survival rate was 91% in the NOM group compared with 95% in the standard surgery group, suggesting that NOM does not compromise outcomes and that preservation of the rectum is achieved in a majority of patients.
Women With Triple-Negative Breast Cancer May Benefit From Nutrition Intervention
Findings from a long-term analysis of the Women’s Intervention Nutrition Study (WINS) showed that the deaths of women with hormone receptor—negative breast cancers were reduced by up to 54% when they followed a program to reduce their dietary fat intake, which could provide benefit for patients with triple-negative breast cancer. Abstract S5-08
Estrogen receptor (ER)-negative patients who followed the program had a reduction of death of 36%, while ER- and progesterone receptor [PR]— negative patients had a 54% reduction of death compared with the control group.
These findings suggest that patients with triple-negative breast cancer, who have an especially poor prognosis, could “substantially increase their chances of survival” through a lifestyle intervention targeting fat intake associated with weight loss, said Rowan Chlebowski, MD, PhD, who announced the results at the 2014 San Antonio Breast Cancer Symposium (SABCS).
The WINS randomized phase III clinical trial was launched in 1994, following comparative studies suggesting a possible link between fat intake and breast cancer: 2437 predominantly postmenopausal women aged 48 to 79 years were recruited from 39 clinical sites across the United States. Study accrual continued from launch until January 2001, and the intervention ended in May 2004. Women were randomized 60:40 within 6 months of diagnosis to either the dietary intervention arm (n = 975) or the control group (n = 1462).
Women in the intervention group were given a fat gram goal by centrally trained, registered dieticians implementing a low-fat eating plan. The women had eight, biweekly individual counseling sessions, with subsequent contacts from a dietitian every 3 months. To monitor their own fat gram intake, women used a “keeping score” book. Patients in the intervention group were supported for a median of 5 years.
After a median 5-year follow-up, researchers saw a 9.2% reduction in fat calories and a 6-pound reduction in weight in the dietary intervention arm. Relapse-free survival was the study’s primary endpoint, and Chlebowski noted that relapse events were 24% lower in the intervention group compared with the control group (9.8% vs 12.4%, respectively).
Although weight loss was not a specific target of the intervention, Chlebowski noted that “when you’re adhering to a low-fat diet, it’s pretty easy to lose some weight, and we saw a statistically significant, consistent 5- to 6-pound weight loss,” in the intervention group.
“In the intervening 20 years, it’s become clear that weight loss is probably more important than dietary fat in terms of influencing breast cancer outcomes,” added Chlebowski, a medical oncologist at the Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center.
The study reported at SABCS provides survival information through 2013, using death registry statistics, thus following only those participants who died. There were 250 deaths in the control group compared with 133 among those who received the intervention. Chlebowski explained that although the death rate was lower in the intervention group (13.6%) compared with controls (17%), the finding was not statistically significant (hazard ratio [HR] = .94). For HR-positive patients, there was also no statistically significant effect from the intervention [HR = 1.01].
Other subgroup analyses yielded significant findings, however, especially in women with ER-negative cancers, who lost weight through the program. Their median survival was 13.6 years versus 11.7 years in the control group, representing 36% fewer deaths.
For the 362 women on the study whose cancers were both ER- and PR-negative, the improved median survival was even more significant in the intervention arm versus controls (14.0 vs 11.7 years, respectively), accounting for a 54% reduction in deaths within this group.
Although the patients’ HER2 status was not available at the time of the study, “it is likely that a substantial number of ER/PR—negative breast cancers were also negative for HER2,” Chlebowski said. Based on recently published SEER data, the percentage of ER/PR-negative patients in the trial estimated to be triplenegative is 73%.
Limitations of the study include the fact that it represents an ad hoc, exploratory analysis, and the subgroup analyses were not preplanned, Chlebowski said. Nevertheless, the findings suggest a favorable lifestyle influence on survival in HR-negative subgroups during active intervention.
“When I look at these results, even with the caveats that you mention, they’re really pretty remarkable in the ER/PR [negative] subset, showing results that reduce the risk of death as good or greater than what we see with our best treatment,” noted press conference moderator Kent Osborne, professor of medicine at the Baylor College of Medicine and director of the Dan L. Duncan Cancer Center.”
Chlebowski said that from a scientific standpoint, “Others will have to look at these exploratory, post hoc analyses and decide whether they warrant support in a further randomized trial to confirm some of these findings.”
From an operational standpoint, he continued, “for a woman with breast cancer, health benefits are associated with a 5%, 5-pound weight loss. We’ve already seen in the randomized clinical trial setting that that amount of weight loss prevents progression from pre-diabetes to diabetes. I think this is something that a woman with breast cancer should consider.”
Laura Newton, MA, RD
Department of Nutrition Sciences
University of Alabama at Birmingham
While this study is not new, from a nutrition perspective, the conclusions presented continue to highlight the overall importance of focusing on weight and weight management as a powerful tool in the prevention of cancer, cancer recurrence, and cancer-related deaths.
Obesity has been linked to poorer cancer outcomes and higher risk of recurrence, particularly in breast cancer. In this study, a reduction in fat intake (which contains more calories per gram than carbohydrate or protein) in the intervention group resulted in a modest weight loss. Various groups such as the American Cancer Society and American Institute for Cancer Research list weight control and management as their top recommendation for cancer survivors.
An optimal dietary pattern for weight loss has not been identified and likely should be individually based. The American Society of Clinical Oncology has published an excellent guide for oncology providers to use to educate patients on the link between obesity and cancer.1 This guide also provides information on assessing weight status, strategies to promote weight loss, and nationally available resources to assist patients and their families with losing weight.
One tool used in the highlighted study to help participants adhere to the intervention was tracking their fat intake with a “keeping score” book. The simple strategy of keeping a food journal is one of the most effective tools in weight management. Although not in cancer patients, a study of overweight, inactive postmenopausal women who followed a calorie-restricted diet for a year found that those who consistently filled out food journals lost about six pounds more than those who didn’t.2 I even use food journals with cancer survivors working to improve the nutritional quality of their diet by incorporating more fruits and vegetables, for example. Writing food intake down forces individuals to think about what they are eating. That process in and of itself can lead to better food choices. Now there are many online programs to help track intake. A benefit to these programs is that many will also calculate the calories from food and even save foods a person normally eats, making it easier next time they pick that item.
Another important takeaway from this study was that the amount of weight loss the intervention group achieved was not unrealistic. Just as for other chronic conditions such as diabetes and heart disease, a weight loss of just 5% may result in significant health benefits. Helping patients set realistic and achievable goals is something all health professionals can do.
- The American Society of Clinical Oncology. Obesity and Cancer. http://www.asco.org/practice-research/obesity- and-cancer. Accessed December 23, 2014.
- Kong A, Beresford SA, Alfano CM, et al. Self-monitoring and eating-related behaviors are associated with 12-month weight loss in postmenopausal overweight-to-obese women J Acad Nutr Diet. 2012;112(9):1428-1435.
Ovarian Suppression Emerges as “Practice-Changing” Option for Premenopausal Breast Cancer Patients
Women with HR-positive breast cancer who remained premenopausal after receiving chemotherapy had a lower risk of disease recurrence when adding ovarian suppression to adjuvant exemestane or—to a lesser extent— tamoxifen compared with standard tamoxifen alone, according to results from the phase III SOFT trial. The data were presented at the 2014 San Antonio Breast Cancer Symposium (SABCS) and simultaneously published online in the New England Journal of Medicine. Abstract S3-08
The more robust exemestane data showed a 35% reduction in the risk of disease recurrence in the premenopausal women treated with the aromatase inhibitor combined with ovarian suppression compared with tamoxifen alone.
“This treatment as compared to standard treatment . . . resulted in 7 or 8 fewer women out of 100 experiencing further breast cancer within the next 5 years,” said Prudence Francis, MD, lead author of the SOFT study, presenting the results at SABCS.
Francis, who is head of Breast Medical Oncology at the Peter MacCallum Cancer Centre in Australia, believes the results will change clinical practice.
“Going forward, I think this is a practicechanging result because what you’ll find is that now, for women who are in this younger, premenopausal age group . . . increasingly doctors will be talking to them about these results and discussing with them the option of undergoing ovarian function suppression treatment with an aromatase inhibitor as an alternative to tamoxifen.”
Francis also noted that the SOFT data were particularly encouraging for “very young” women (aged <35 years), who have a higher risk of recurrence with hormone sensitive breast cancers. The benefit of adding ovarian suppression to exemestane was most pronounced in this population.
“One in three women receiving tamoxifen alone experienced further breast cancer within 5 years as compared with one in six of the women assigned to exemestane plus ovarian suppression.”
Not all women in the SOFT trial benefitted from ovarian suppression, however. Patients were stratified by receipt of chemotherapy, and women in the chemotherapy-naïve cohort did well whether they received tamoxifen alone or ovarian suppression combined with either tamoxifen or exemestane. “These women have had excellent outcomes with all three treatments, and we see no advantage for adding ovarian suppression in this group,” said Francis.
The SOFT trial data presented at SABCS included 3047 premenopausal women with early HR-positive breast cancer randomized to 5 years of tamoxifen (n = 1018) or ovarian function suppression (OFS) added to either tamoxifen (n = 1015) or exemestane (n = 1014).
Ovarian suppression was achieved by choice of monthly triptorelin injections, bilateral oophorectomy, or bilateral ovarian irradiation. Patients initially administered triptorelin were allowed to subsequently undergo surgery or receive radiation. Fifty-three percent of patients (n = 1628) had received prior adjuvant or neoadjuvant chemotherapy and remained premenopausal. These women were younger (average age, 40 years) and had higher-risk tumors. Patients in this cohort were allowed to enter the study up to 8 months after completing chemotherapy. During those 8 months, patients could receive tamoxifen. To enter the trial, women had to have a blood test measuring their estrogen levels to demonstrate that their ovaries were still functioning.
The remaining 47% of women (n = 1419) were chemotherapy-naïve. These patients tended to have lower-risk breast cancers and were older (average age, 46 years). They entered the study within 12 weeks of surgery and tamoxifen was their only systemic therapy.
The primary SOFT analysis compared tamoxifen with tamoxifen plus OFS across both chemotherapy cohorts. According to Francis, “At a median follow-up of 5.6 years, we saw that adding ovarian suppression to tamoxifen resulted in a small but not significant improvement in disease-free survival [DFS]” (86.6% vs 84.7%; HR = .83; 95% CI, 0.66-1.04; P = .10).
In the chemotherapy cohort, adding tamoxifen to OFS reduced the risk of disease recurrence by 22% versus tamoxifen alone (HR = .78; 95% CI, 0.60-1.02). Further benefit was observed with exemestane, which had an HR for DFS of 0.65 when combined with OFS versus treatment with standard tamoxifen (95% CI, 0.49-0.87).
In the lower-risk, chemotherapy-naïve cohort, the 5-year DFS was 95.8% with tamoxifen alone, compared with 95.1% with tamoxifen plus OFS (HR = 0.95; 95% CI, 0.54-1.69) and 97.1% with exemestane plus OFS (HR = 0.59; 95% CI, 0.31- 1.14).
“One of the important things we’ve also learned from this study is that this lower risk group can actually do very well with tamoxifen alone,” said Francis
Among the 350 women aged <35 years in the overall study population, 94% of whom had received chemotherapy, the 5 year—DFS rates were 83.4% (95% CI, 74.9-89.3), 78.9% (95% CI, 69.8-85.5), and 67.7% (95% CI, 57.3-76.0), respectively, for patients treated with exemestane plus OFS, tamoxifen plus OFS, and tamoxifen alone.
Francis said the benefit with OFS observed in these younger patients is critical because they are unlikely to be able to wait for the benefit that has been established with long-term hormonal therapy. “This youngest group is having the breast cancer events early [within the first 5 years] and it’s too long to wait to see if the extended hormonal therapy might benefit them because they may have already had a distant relapse by that time.”
The toxicity profile in the study was acceptable, according to Francis. “Overall quality of life and general health were not reduced,” she said. “However, ovarian suppression did result in increased menopausal symptoms, which were particularly troublesome for the women in the first couple of years.” Additionally, women receiving exemestane plus OFS had side effects related to sexual functioning.
Francis noted that strictly ensuring the HR sensitivity and premenopausal status of patients enrolled in the SOFT trial was critical to obtaining the observed benefit of ovarian suppression in the trial. “In previous trials, the effect of ovarian suppression has really been diluted because some women went into those trials with uncertain hormone-receptor status of their breast cancer, so there were a mix of hormone receptor positive and negative. Also, women went into those trials straight after chemotherapy, and many of them were probably permanently postmenopausal from the treatment, so any effect from ovarian suppression was diluted.”
The next step for the SOFT trial, said Francis, will be to determine how these different treatments will affect overall survival.
In her summary, Francis reiterated her belief that the results are practice changing.
“For me, if I go back to my practice on Monday, and I see a woman under 35 with a hormone sensitive breast cancer, I will now know what to advise that woman. Also, when I see the woman who is 48 and has a small, nonaggressive breast cancer, I will feel more comfortable that she can do very well with tamoxifen alone.”
Emily Beard, RN, OCN, CBCN
Women’s Oncology Program
Northside Hospital Cancer Institute
The benefits of adjuvant hormonal therapy for some women with breast cancer are well documented, as is understanding that the function of the premenopausal ovaries puts certain women at risk for disease recurrence. But until now the question lingered: which women got the greatest benefit from suppressing ovarian function? These latest SOFT trial data provide important information to sort this out and invite more questions and considerations for clinicians caring for these patients.
So now we know that there are specific groups—young women 35 years and younger— who derive a tremendous benefit from ovarian suppression when combined with an aromatase inhibitor or tamoxifen, and some for whom there is no clinical benefit (and thus no need to expose them to the side effects of the treatment).
This is great news in terms of impact on survival, but the choice to suppress ovarian function, particularly in a young woman, has tremendous quality of life implications. These patients tolerate vasomotor symptoms, vaginal dryness, decreased libido, fertility concerns, and joint pain that unfortunately come at a time when many are entering intimate relationships, starting or expanding families, and desire to be physically active in the workplace and at home. They often need encouragement and interventions to successfully maintain their prescribed regimen.
Clinicians must have open dialogue with patients and be willing to provide emotional support in order to encourage patients to stay on their medications. I have heard from many a patient who stopped her treatment, knowing full well it could impact her survival, because the side effects were too extreme.
In this dawning era of personalized medicine where the breast cancer dialogue increasingly involves discussions about overtreatment, targeted therapies, and reducing toxicities in long-term survivors, these results give us a hopeful place to start having conversations with our patients (and each other) about what options are available and what the consequences of those options may be.
Brentuximab Vedotin Delivers Unprecedented Posttransplant PFS Benefit in Relapsed Hodgkin Lymphoma
Following treatment with high-dose chemotherapy and stem cell transplant, patients with relapsed and difficult- to-treat Hodgkin lymphoma who received brentuximab vedotin had an unprecedented 50% higher likelihood of continuing to experience progression- free survival (PFS) at 2 years. This is particularly meaningful because most patients in this population who haven’t experienced relapse 2 years after transplant are cured. Abstract 673
The study’s lead author, Craig Moskowitz, MD, of Memorial Sloan Kettering Cancer Center, reported those results from the phase III, placebo controlled AETHERA trial at the 2014 American Society of Hematology (ASH) Meeting.
While roughly half of patients with this condition are cured through the administration of high-dose chemotherapy and stem cell transplant, maintenance strategies to prolong good health afterward are needed because many others relapse, Moskowitz said.
Brentuximab vedotin is an antibody that targets the CD30 protein on Hodgkin lymphoma cells. The drug has demonstrated an objective response rate of 75% in Hodgkin lymphoma that has relapsed or become refractory after autologous stem cell transplant; the AETHERA trial was initiated to evaluate whether early treatment with brentuximab vedotin after transplant could prevent progression in patients with Hodgkin lymphoma, the authors wrote in the abstract presented at ASH.
“This is the first study in lymphoma to demonstrate that the addition of a maintenance drug after transplant can markedly improve patient outcomes,” Moskowitz said. “Given these extremely positive results, we predict that brentuximab vedotin will soon become the standard of care for Hodgkin lymphoma patients who undergo an autologous stem cell transplant.”
The randomized, multicenter study compared brentuximab vedotin with placebo in 327 patients who had been treated with a minimum of two prior systemic therapies and faced a risk of posttransplant disease progression. All had either achieved remission or had stable, nonprogressing disease at the time of stem cell transplant. Thirty to 45 days after transplant, patients were randomized to receive best supportive care plus either 1.8 mg/kg of brentuximab vedotin or placebo every 3 weeks for up to 16 cycles (approximately 1 year). Patients on the placebo arm who experienced disease progression were allowed to leave the trial and receive brentuximab vedotin as part of a different study.
After a median follow up of 2 years, 65% of patients receiving the drug were still experiencing PFS compared with 45% of patients receiving placebo. In an analysis of blinded, pooled efficacy data, an independent review board found that 63% of patients with Hodgkin lymphoma and risk factors for relapse or progression had continued PFS at 2 years when taking brentuximab vedotin, compared with 51% for those on placebo, meaning that, for the overall study population, the 2-year PFS rate was 54%.
Overall survival, at a rate of 88% at 2 years, was the same in both arms, although that number was confounded by the fact that 85% of patients left the placebo arm to receive brentuximab vedotin, and some patients, upon disease progression, underwent second transplants and were salvaged, Moskowitz said.
The median number of treatment cycles was 15, or about 11 months, and 159 patients received 16 cycles. Reasons patients discontinued treatment included disease progression (n = 93), adverse event (n = 61), patient decision (n = 15), and investigator decision (n = 1).
The most common side effects associated with brentuximab vedotin were peripheral sensory neuropathy, upper respiratory tract infection, neutropenia, fatigue, cough, and pyrexia. These were mostly manageable through dose reductions or delays. There were 50 deaths over the 2-year study period, eight occurring prior to disease progression; two deaths occurred within 40 days of dosing with brentuximab vedotin, the authors reported.
Phyllis McKiernan, MSN, APN, OCN
Blood and Marrow Transplant Programs
John Theurer Cancer Center
For patients with relapsed Hodgkin lymphoma (HL), the standard treatment is salvage chemotherapy followed by high-dose chemotherapy and autologous stem cell transplant, with approximately 50% of patients cured using this approach. Patients with chemosensitive disease have improved posttransplant outcomes over patients who do not respond to salvage therapy (ISRN Oncol. 2014. doi:10.1155/2014/605691). Other high-risk factors include positron emission tomography (PET) positivity postsalvage and extranodal disease.
There are salvage therapies for relapsed HL after autologous transplant, including the use of targeted therapy such as brentuximab vedotin. With a demonstrated response rate of 75%, the drug shows significant activity in relapsed HL posttransplantation. Strategies to prevent relapse after autologous transplant include the use of maintenance therapy. Therefore, the question was raised if posttransplant brentuximab vedotin could improve outcomes by preventing relapse in high risk HL patients.
The results of the study showed the addition of brentuximab vedotin did improve progression-free survival (PFS) after transplant for HL, supporting the role of maintenance therapy. This approach is being explored in other hematologic malignancies posttransplant, including non-Hodgkin lymphoma, leukemia, and multiple myeloma. While improved survival is the ultimate goal, maintenance therapy has other implications for patients, including prolonged treatments and potential side effects. This could have a financial impact for patients unable to return to work during maintenance.
The side effects of brentuximab vedotin, while manageable with dose reductions and treatment delays, can lead to serious complications such as infection, dermatologic reactions, and severe peripheral neuropathy. Vigilant clinical monitoring, side effect management, and assisting patients with establishing a routine that fits their lifestyle may improve adherence and increase the likelihood of therapy completion.
The shift toward maintenance therapy after transplant is likely to continue as positive studies emerge, and nurses will play a pivotal role in navigating patients through the process.
Higher Vitamin D Levels Improve Survival for Patients With mCRC
Patients with newly diagnosed metastatic colorectal cancer (mCRC) who had higher levels of vitamin D in their blood lived a median of 8 months longer and experienced greater disease-free survival after their cancer treatment, according to research reported at the 2015 Gastrointestinal Cancers Symposium. Abstract 507
The study found that those with the highest levels of vitamin D (average 27.5 ng/mL) had a median overall survival of 32.6 months compared with 24.5 months among patients with the lowest levels (average 8 ng/mL; HR = 0.67; CI 95%, 0.53-0.86; P = .002). Higher vitamin D levels were also associated with longer time to disease progression (12.2 months in the group with the highest levels vs 10.1 months in those with the lowest (HR = 0.80; CI 95%, 0.64-1.01; P = .02).
If the association is confirmed in randomized phase III trials that are currently recruiting participants, vitamin D supplementation could become standard care in this setting, noted lead study author Kimmie Ng, MD, MPH. Ng, assistant professor of medicine at Dana-Farber Cancer Institute, is the lead investigator on one of these studies (NCT01516261) comparing standard mCRC treatment with and without vitamin D supplementation.
Vitamin D is known to inhibit cell proliferation and angiogenesis and has anti-inflammatory effects. Although multiple prospective studies have suggested that higher levels of 25-hydroxyvitamin D (25[OH]D) are associated with decreased risk and improved survival in CRC, it was not known whether this association also would hold true for patients with metastatic disease who are commonly vitamin D-deficient.
In the study reported here, baseline 25(OH) D levels were determined through pretreatment blood samples collected from 1043 patients enrolled in the CALGB/SWOG 80405 trial, comparing frontline therapy with bevacizumab or cetuximab combined with FOLFOX or FOLFIRI in patients with KRAS wild-type mCRC. Participants also completed a questionnaire about their dietary and lifestyle behaviors.
Investigators determined that the median vitamin D level was 17.2 (range 2.2-72.2 ng/mL). The recommended healthy range for vitamin D is 20-30 ng/mL.
The researchers noted that overall, very few study participants reported vitamin D supplementation. Older age, black race, lower dietary and supplemental vitamin D intake, higher body mass index, worse general physical condition, and lower physical activity were all associated with lower vitamin D levels.
Ng said that after adjusting for multiple known prognostic factors as well as potential confounders, the significant relationship between higher vitamin D levels and improved overall and progression-free survival persisted.
Furthermore, said Ng, “The benefit of higher vitamin D levels on overall survival was seen across all subgroups examined,” and no significant differences were observed with regard to the type of therapy the patients received.
“This study will be of great interest to patients with colorectal cancer who frequently want to know if there is anything they can do besides chemotherapy to improve their outcomes,” said symposium press session moderator Smitha S. Krishnamurthi, MD, associate professor of medicine at Case Western Reserve School of Medicine. “This study adds to the literature that suggests that vitamin D may have protective effects in preventing colorectal polyps and help patients with colorectal cancer live longer.”
Notably, Krishnamurthi continued, “patients in this study with the highest vitamin D levels had the longest survival. Progression-free survival also improved, suggesting that high vitamin D levels may lead to a slower-growing tumor or could enhance the effects of chemotherapy.”
&Experts agree that patients should have their vitamin D levels checked and have supplementation if needed.
“It is too early to recommend vitamin D as a treatment for colon cancer, but we do know that maintaining adequate vitamin D levels has other health benefits, such as for bone health,” concluded Ng.
Laura Metcalfe, MSN, RN, APN-C, AOCNS
John Theurer Cancer Center
I was very interested to read the results of this study. Over 20 years ago the importance of vitamin D from sunlight in preventing colorectal cancer was recognized. Significantly higher mortality rates from colorectal cancer were observed in the northern and northeastern United States compared with the southwest, Hawaii, and Florida. This correlated directly with an individual’s vitamin D status; that is, people who had higher levels of serum vitamin D had lower rates of colon cancer. In addition, reduced risk of colorectal cancer recurrence has been associated with higher vitamin D levels. As explained in this article, this makes sense given that vitamin D inhibits cell proliferation and angiogenesis and that it has anti-inflammatory effects
For many years it has been our practice to advise our colorectal cancer survivors to take vitamin D supplements to minimize their risk of recurrence. We have done this with Stage I, II and III patients; ie, those who never needed chemotherapy or those who have completed their adjuvant chemotherapy. Our target is a level >40 ng/mL. To start, we recommend taking vitamin D 2000 IU daily. If, after 3 months, their level is not at or above 40 ng/mL, we increase the dose to 50,000 IU weekly, given by prescription. We have not routinely monitored vitamin D levels or recommended taking vitamin D to those patients with metastatic disease as there were not data to suggest it would benefit them…until now.
This study found a longer median overall survival and a longer time to disease progression in those with the highest vitamin D levels among patients newly diagnosed with metastatic colorectal cancer. These results suggest that high vitamin D levels may lead to a slower-growing tumor or might enhance the effects of chemotherapy.
Either way, I believe this will change our practice in that we will now monitor levels and recommend vitamin D supplementation for patients with metastatic colorectal cancer. As oncology nurses, we try to empower our patients to be active participants in their care as well as helping them to achieve their best outcome. This seemingly simple intervention of taking vitamin D may actually help us achieve both of those goals.
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