While there weren’t new blockbuster announcements for colorectal cancer this year at the American Society for Clinical Oncology’s (ASCO) Annual Meeting, there was plenty of focus on making what we already have work better and on choosing the patients who will benefit the most from treatments, as well as those who might not be helped at all. (Note, many of these issues will be discussed in detail on our upcoming patient webinar.)

Highlights:

• While adding oxaliplatin to 5-FU improves five year survival slightly for stage II colon cancer, it increases side effects, particularly tingling and numbness in the feet.  An analysis of several NSABP trials found that two or three more stage II patients out of every 100 would be alive five years later if they were given oxaliplatin in addition to 5-FU than if they only got 5-FU.  Risk of cancer returning was similar with an absolute improvement of 3 to 5 percent, depending on risk factors.  Doctors and patients need to think about whether the small benefit is worth the risk of neuropathy that may become permanent.
• Two speakers at the Saturday colorectal cancer oral abstract session addressed adding oxaliplatin to 5-FU as part of pre-surgical chemoradiation treatment for rectal cancer.  NSABP R-04 found that oxaliplatin did not help increase complete response rates, avoid colostomies, or downstage cancers. It did increase diarrhea significantly. On the other hand, early results from a German trial did find an increase in complete responses with oxaliplatin, and they didn’t see worse side effects.
• In the PRIME phase III clinical trial, patients receiving their first treatment for advanced colorectal cancer who had normal or wild-type KRAS genes in their tumor did better when Vectibix® (panitumumab) was added to FOLFOX chemotherapy.  But those patients whose tumor KRAS was mutated actually did worse than patients who only got chemotherapy.
• Side effects, while difficult for patients, may predict better outcomes from treatment.  Patients who got capecitabine as part of pre-surgical chemoradiation and developed hand-foot syndrome had fewer recurrences three years later and better survival at five years.  In another study of breast, lung, and colorectal cancer, patients who got high blood pressure while on Avastin® (bevacizumab) lived longer and it took longer before their cancer got worse.

The Cost of Cancer Care

In an editorial in the ASCO Daily News, published every day for ASCO attendees, Jeffrey M. Peppercorn, MD, MPH, discussed the rising out-of-pocket costs of cancer care for patients and their families.  Although cancer care costs overall are growing fast, the costs that patients bear are growing even faster.  About a third of cancer patients say they have trouble paying their bills, and one out of four have exhausted their savings.

Although the ASCO Task Force on Cost of Cancer Care calls for oncologists to discuss out-of-pocket expenses with patients, few do, and a survey found that about half of oncologists are uncomfortable talking about costs in deciding on treatment.

To learn more, join us for our next patient webinar:

The Big News in Colorectal Cancer from the 2011 ASCO Annual Meeting
June 20, 2011
8 – 9 PM Eastern time
Register to join us.

 

Colorectal cancer patients getting oxaliplatin quickly learn to avoid cold. Drinks with ice, chilly air, even opening the freezer can produce sudden, sharp pain, burning, or an unpleasant pins and needle feeling in their throat and hands.

A small study has found that venlafaxine (Effexor) can completely eliminate acute neurotoxicity from oxaliplatin in about 1 out of 3 people.  More than half of patients who took it had more than 50 percent relief from symptoms.

In the trial, 48 patients who were already having pain after oxaliplatin infusions were randomly assigned to get 50 mg of immediate release venlafaxine an hour before their treatment or a placebo.  They then took an extended release venlafaxine capsule or a placebo twice a day for the next ten days, stopping the medicine two days before their next oxaliplatin treatment.

They rated their symptoms on the day of treatment and four days after it using the Neuropathic Pain Symptom Inventory (NPSI), a scale that rates 12 neurosensory feelings (for instance, burning pain, pins and needles,pain made worse by cold,pain like electric shocks, pain that is worse when something touches you).  They also reported changes in function — how well they could use their hands or feet.

Results

• 31.3 percent of patients taking venlafaxine had complete relief of symptoms compared to 5.3 percent of those on placebo.
• 58.8 percent of patients had some relief, at least 50 percent, of symptoms compared to 26.3 percent of those taking a placebo.
• None on venlafaxine had grade 3 acute neuropathy with serious pain, loss of feeling, or loss of function while 33.3 percent of those on placebo did.

Venlafaxine also improved problems with pins and needles and functioning.

There were no serious side effects for those taking the medicine.  The most common side effects were mild to moderate feelings of general weakness and nausea.

While the study showed that venlafaxine may be helpful in reducing acute neurotoxicity from oxaliplatin, it was small.  Larger trials are necessary before its safety and effectiveness can be reliably demonstrated.

Effexor® (venlafaxine) is approved by the FDA to treat depression and anxiety disorders.  While it is sometimes used off-label to treat other conditions, including diabetic neuropathy, it is not approved for acute neuropathy from oxaliplatin treatment.  Like other anti-depressants that are similar to it, it carries a warning box on its label for risk of suicidal feelings.  It may interact with a number of prescription medicines as well as some herbal products, including St. John’s Wort.

SOURCE: Durand et al., Annals of Oncology, Advance Access, March 22, 2011.

We need to monitor not only for liver function but also for kidney function. However kidney problems are much less frequent.

Patients who undergo chemotherapy know that every time they receive chemotherapy, oncologists take blood to test for blood counts and also for liver and kidney function.

There are many drugs which need their doses reduced or treatment held held if the kidney function changes. One of the common mistakes is that Xeloda, the oral 5-FU drug used for colon cancer, does need to have its dose reduced for kidney dysfunctions. However 5-FU and oxaliplatin don’t have to be dose reduced, which is astonishing since cisplatin has tremendous kidney toxicities which oxaliplatin does not.

Avastin needs to closely monitored for kidney toxicities. Rarely patients can develop proteinuria, which means the kidney loses too much protein. In this situation Avastin needs to be stopped. This is usually reversible within weeks. Proteinuria has been well described, particularly in patients with renal cancer. We have seen proteinuria in patients with colorectal cancer treated with Avastin, which is the reason we check a urinanalysis every 4 weeks to make sure there is no significant protein in the urine.

Patients can monitor proteinuria at home. Whenever there is a lot of protein in the urine, urine foams and makes a lot of bubbles in the toilet. Let your doctor know if this is happening.

Erbitux has also some toxicity to the kidney. It is very rare but needs to be monitored too. It can make the kidney loose magnesium. Your oncologist should test magnesium levels in the blood at every visit. Clinically patients can experience cramping in their legs and hands or can feel lethargic. Make sure magnesium levels are within normal range. This is particular important for patients who have diarrhea who may lose additional magnesium in the stool. If any of these symptoms occur you need to contact your oncologist to work you up.

In my own practice we have a number of patients who are on dialysis and treated effectively with chemotherapy. This is possible depending on the amount of the drugs being eliminated by the dialysis. Usually we treat these patients after their dialysis to allow optimal exposure of drugs to the tumor. Please discuss this with your oncologist if you have a chronic renal failure.

One of the problems for patients who have some increased creatinine levels is using contrast agents when they undergo CT scans. With any decreased kidney function you need to be very careful using IV contrast which can be harmful to your kidney. Discuss this with your oncologist.

Again for patients with kidney dysfunction, we offer very specific clinical trials which should consider if you do not qualify for other clinical trials.

Cancer patients are often very tired, a bone-weary fatigue that doesn’t get better with rest.  Fatigue is the most common complaint from patients during chemotherapy.  However, a recent study found that one in four patients are already severely fatigued before treatment ever begins.

Severe fatigue was most common in patients with gastrointestinal cancer, where almost one in three were fatigued at diagnosis.

Contributing to initial serious fatigue were:

• Lack of physical activity
• Depression
• Poor sleep and rest patterns during the day and night
• Fatigue existing a year before diagnosis

Dr. M.M. Goedendorp and her colleagues at the Expert Centre for Chronic Fatigue in Nijmegan, The Netherlands, concluded,

Relatively large numbers of cancer patients already experience severe fatigue before initiation of treatment, varying between 14–28%. The factors that contributed to severe fatigue at this stage were physical activity, depressive mood, impaired sleep and rest, and fatigue 1 year before diagnosis.

SOURCE: Goedendorp et al.,British Journal of Cancer, published online October 21, 2008.

Five randomized studies have shown that chewing gum after colon surgery reduces the time it takes for patients to pass gas and have a bowel movement.

Patients in the studies chewed sugarless gum from 5 to 45 minutes, three times a day after surgery.  Control groups had similar surgeries but didn’t chew gum.

There was a trend toward leaving the hospital sooner, but the studies were too small to definitely show fewer hospital days for the gum chewers.

Still, the study authors wrote,

The potential cost savings from the reduction of even one postoperative day compared with the cost of several sticks of chewing gum are huge.

During intestinal surgery, the bowels stop moving contents forward, a situation known as ileus.  After surgery doctors listen for sounds in the bowel and wait for gas to pass through the rectum as signs that bowel activity is resuming.

Overall in the five studies, patients who chewed gum passed gas about half a day sooner and had their first bowel movement a day sooner.

The team concluded,

Chewing gum may enhance intestinal recoveryfollowing colectomy and reduce the length of hospital stay. Owing to the potential for substantial cost savings, larger-scale,blinded, randomized controlled trials with placebo arms are warranted.

Previously, C3 News has reported post-surgical gum chewing studies in California and Dallas and Pittsburgh.

More information about the overview of gum studies is on Medpage Today.

SOURCE: Purkayastha et al., Archives of Surgery, Volume 143, Number 8, August, 2008.

The Food and Drug Administration has approved an oral formulation of Aloxi® (palonosetron) to prevent nausea and vomiting from chemotherapy.  A single 5 milligram capsule reduces the risk of nausea during the first 24 hours after chemotherapy and for up to five days afterwards.  The medicine is taken about an hour before chemotherapy starts.

The most common side effects were headache, experienced by about four percent of patients and constipation in less than one percent.

Information from the FDA about the new oral Aloxi approval.

Intravenous Aloxi has been available since 2003 to manage both acute nausea and vomiting in the hours after chemotherapy and delayed nausea during following days.

The patient brochure for IV Aloxi provides additional help to manage chemotherapy-induced nausea including avoiding:

• Solid food right before and after treatment
• Caffeine and alcohol
• Spicy or greasy foods
• Cooking odors, smoke, perfume
• Your favorite foods after receiving chemotherapy so they don’t become triggers for nausea
• Unpleasant sights, sounds, and smells that might trigger nausea
• strenuous exercise

The brochure also suggests

• Eat lightly on the day of treatment.
• Eat several small meals during the day instead
  of large ones.
• Drink cool, clear fluids, such as sports drinks,
  ginger ale, or lemon-lime sodas.
• Eat foods that are cool or at room temperature.
• Eat bland foods (dry toast or soda crackers).
• Take care of your mouth.
• Take part in hobbies or practice relaxation techniques.

The makers of Aloxi also provide a calendar that helps patients record vomiting, nausea, and how they felt in the days after chemotherapy.  The information can then be shared with the doctor or oncology nurse.

Occasionally people having CT scans or other imaging exams will have an allergic-type reaction to the iodine contrast, but research has found that they can be treated safely without long term effects. In fact, almost all reactions are mild and more han 99 percent patients with them will get better within a day.

Radiologists at the University of Michigan hospitals in Ann Arbor studied nearly 85,000 intravenous injections of nonionic iodinated contrast media looking for allergic-type reactions.  They analyzed both how the reactions were treated and whether there were any long term problems after a reaction.

They found that reactions were rare — 545 or about half a percent of all patients had some allergic-type reaction with 221 requiring treatment. Most were mild (418), some moderate (116), and 11 were severe.

Almost all — 99 percent — had symptoms go away within 24 hours.  Only two patients, who had severe reactions, had problems lasting more than a day.

The most common treatment was Benedryl® (diphenhydramine) given to 145 patients.  A few received corticosteroids, albuterol or ephinephine.

Although outcomes were generally very positive, the research team was concerned that errors were made in treating patients who had reactions.  Richard Cohan, MD, who led the study, commented,

Commonly used medications can be administered safely; however, treatment errors are not uncommon and in a few instances can lead to patient morbidity. In our study, we found a number of instances in which non-recommended treatment was provided. These cases included the administration of oxygen by nasal cannula (rather than mask) and at lower than recommended doses, over-utilization of diphenhydramine (including to a few patients who were hypotensive), and the administration of higher than recommended doses of epinephrine, as well as occasional confusion about which concentrations of epinephrine should be injected in which manner (subcutaneously or intravenously).

Dr. Cohan suggested that radiology teams regularly review recommendations and plans for managing allergic reactions to contrast material,

We hope that after reading our study, radiologists, nurses, and technologists will agree that they must review the algorithms for treating contrast reactions on a regular basis (particularly issues related to diphenhydramine, oxygen, and epinephrine administration. In fact, we would suggest that such a review should probably occur at least twice a year. However, it is also consoling to know that even when patients have moderate or severe contrast reactions, the vast majority recover promptly and without any long term complications.

SOURCE:  Cohan et al., American Journal of Roentgenology, Volume 91, Issue 2, August 2008.

An immediate switch from 5-FU treatment to Xeloda® (capecitabine) for stage III colon cancer caused so much toxicity that a trial designed to test patient preferences for treatment had to be stopped.

Patients in the Patient Preference in Adjuvant Therapy (PACT) trial who switched after 6 weeks from weekly 5-FU with leucovorin to oral capecitabine experienced excessive side effects. The trial was designed to determine which approach to treatment patients liked best.

Patients were randomized to two groups:  the first group began treatment with weekly intravenous 5-FU and leucovorin for 6 weeks (start period) and then switched to oral Xeloda for six weeks (switch period).  The second group began with Xeloda during the start period and got 5-FU during the switch period. Finally, patients would choose the treatment they preferred to complete the final 12 weeks of treatment (preference period.)

However, the trial was halted after 40 of a planned 74 patients were enrolled because of the high toxicity in the first group who made the 5-FU to Xeloda switch.  Serious grade 3 or higher side effects in those now getting Xeloda included diarrhea, hand-foot syndrome, and lethargy.  One patient had low white counts with blood infection, and one experienced angina.

During the start period:

• The Xeloda group had moderately higher percentages of severe (grade 3 or higher) side effects than the 5-FU group (28 percent versus 0 percent)
• 44 percent of the Xeloda group required a lower dose or postponed treatments compared to 6 percent of the 5FU group.

Durng the switch period:

• 79 percent of the 5-FU patients who switched to Xeloda had severe grade 3 side effects compared to none of the patients who switched from Xeloda to 5FU.
• Only 2 of 14 5-FU patients who switched to Xeloda were able to tolerate the full dose.

During the preference period:

20 patients reached the end of the twelfth week of treatment before the study was closed and were able to make a choice of which treatment they preferred.

• 3 patients, who had taken Xeloda in the switch period, had already dropped out of treatment entirely because of severe side effects.
• 5 patients chose to return to Xeloda.  All 5 had taken Xeloda in the start period, switched to 5-FU, and now wanted to return to Xeloda.
• 4 of those 5 patients who returned to Xeloda after the switch period on 5-FU developed severe side effects during the preference period.
• 2 of 12 patients (17 percent) choosing 5-FU developed severe side effects.
• 1 patient, who had been in the original Xeloda arm during the start period and had switched to 5FU, asked to return to Xeloda.  Despite not having side effects from Xeloda during the start period, she developed serious side effects, had a heart attack, and died.

The researchers don’t know the reason that the sequence of 5-FU with leucovorin and Xeloda made such a startling difference in side effects, but they think that leucovorin (folic acid) may be at the bottom of the mystery.  It is possible that leucovorin allows folate to build up in cells and contributes to more serious side effects when Xeloda is begun.

They point out the recent studies that found more side effects from 5-FU and Xeloda in the United States where food is fortified with folic acid.

Although this study looked specifically at treatments that used 5-FU and leucovorin or Xeloda alone, the researchers believe that doctors should also take care with switching combination therapies.

This caution should also be extended to switching patients from combination regimens containing FU/LV to capecitabine-containing equivalents (eg, from infusional FU/LV with oxaliplatin to capecitabine with oxaliplatin).

The team, headed by Dr. Ivo M. Hennig, concluded,

In chemotherapy-naive patients, capecitabine produced more toxicity than FU/LV, but at levels in line with previously reported data. However, treatment with capecitabine after FU/LV caused markedly increased toxicity, indicating a sequence-specific interaction. The mechanism has not been determined, but interaction with intracellularly retained folate after FU/LV therapy is a possibility. Oncologists need to be aware of this risk if considering crossing patients over from FU/LV to capecitabine-based regimens.

SOURCE: Hennig et al., Journal of Clinical Oncology, Volume 26, Number 20, July 10, 2008.

What this means for patients

Patients need to be aware that an immediate switch from intravenous 5-FU given with leucovorin and Xeloda (capecitabine) may be dangerous.  They should discuss such switches carefully with their oncologists.

Because folate in cells may be the reason for increased serious side effects, patients should discuss all sources of supplementary folic acid with their doctors, including that in enriched foods and multivitamins.

The National Institutes of Health Office of Dietary Supplements has more information about folate in food and folic acid supplements.

Cancer treatment can make it hard to eat.  Both chemotherapy and radiation treatment can cause mouth sores, dry mouth, or poor appetite. Some patients develop thrush, a fungus infection in their mouths and throats, that makes swallowing very painful.

Traditionally canned or powdered nutritional supplement drinks like Ensure® or Boost® have been used to provide support to patients who are having trouble eating during treatment.

As an alternative, soft whip ice cream machines were installed on oncology wards in a hospital in the United Kingdom.  The machines served a premium ice cream which had comparable protein to the nutritional drinks.

Patients were asked to compare the new ice cream to the regular ice cream served by the hospital and to the nutritional drinks.  Results of the patient survey found:

• 74 percent rated the new ice cream tasted good or excellent.
• 78 percent said that it was easy to eat.
• 77 percent preferred the new soft whipped ice cream to regular hospital ice cream.
• 88 percent preferred the new ice cream to nutritional drinks.

The researchers pointed out the importance of having supportive supplements that patients enjoyed and would eat.

The team, led by C.L. Wright, concluded,

The use of ice cream illustrates a positive way forward for the dietetic treatment of malnutrition in cancer patients and further work is planned for the future. The use of branded ice creams provides an acceptable alternative to oral nutritional supplements in cancer patients with chemotherapy and radiotherapy associated mouth problems.

SOURCE: Wright et al.,Journal of Human Nutrition and Dietetics, Volume 21, Number 4, August 2008/

What This Means for Patients

Soft serve ice cream may provide an alternative to nutritional drinks for patients who have difficulty eating.

Discuss it as a possibility with a nutritionist or your doctor.

Cold foods, like ice cream, may cause sudden pain or a feeling that the throat is closing and you can’t get a breath in the days after treatment with Eloxatin® (oxaliplatin).  You should avoid cold foods and drinks during this time.

Nearly all patients who are treated with Vectibix™ (panitumumab) will develop an itchy skin rash that looks something like acne.  However, treating the rash preemptively  before it appears reduces its severity and lengthens the time before more serious rash appears.

During the STEPP (Skin Toxicity Evaluation Protocol with Panitumumab) trial, researchers randomized patients who were being treated with Vectibix to either preemptive skin rash management at the beginning of chemotherapy or reactive treatment once rash appeared.  After six weeks, 70 percent of patients treated preemptively had not developed grade 2 skin rash.  Sixty-two percent of the reactive group already had rash that was grade 2 or higher.

Skin rash management included:

• Moisturizers
• Sunscreen
• Topical steroids
• Oral doxycycline

After six weeks of treatment, 70 percent of the preemptive group were free of grade 2 rash, while only 38 percent of the reactive group were rash-free.  In the reactive group half of patients had developed a grade 2 rash by 2.7 weeks.

More than twice as many people in the reactive group developed a more severe grade 3 rash (62 percent in reactive group versus 29 percent of the preemptive group.)

There was no increase in other side effects in the preemptive group.

Patients in the study were either treated with FOLFIRI chemotherapy and Vectibix every two weeks or Camptosar® (irinotecan) and Vectibix every three weeks.

As in other studies, benefits of Vectibix treatment were limited to patients without KRAS mutations in their tumors (wild-type).

Reflecting on the results of the STEPP study, David Chang, M.D., vice president for oncology clinical development at Amgen said,

Since skin rash is the most common side effect of EGFr therapy, the results of the STEPP trial showing that skin rash may be controlled by a relatively simple preemptive treatment, represent a significant advancement.

STEPP results were presented during the World Congress on Gastrointestinal Cancer in Barcelona, Spain.