Surviving Chemotherapy for Colon Cancer and Living with the Consequences

Introduction

In June 2006, at the age of 68, Sue was diagnosed with stage IIIA colon cancer after a colonoscopy revealed a mass in the ascending colon. She underwent right colectomy followed by 12 treatments with FOLFOX 4, a chemotherapy regimen containing oxaliplatin, 5-fluorouracil, and leucovorin. Her adjuvant chemotherapy started in July 2006 and ended in January 2007. Aside from occasional nausea and vomiting, fatigue, and occasional insomnia and development of mild numbness and tingling in the hands and feet, Sue tolerated her chemotherapy well. During her chemotherapy, the side effects she experienced had little effect on her daily activities.

In April 2007, 3 months after she completed her chemotherapy, she started experiencing debilitating symptoms. The numbness and tingling in her hands and feet became progressively more severe and she developed profound fatigue, muscle weakness, dizziness, and loss of muscle tone. She was unable to rest comfortably or get comfortable. In addition, her appetite was poor, she had frequent nausea, and was losing weight. These symptoms, coupled with lack of sleep left her feeling depressed but she was hopeful that these were temporary problems that would soon resolve. Her oncologist also was hopeful that these delayed side effects would soon resolve.

She does not recall anyone explaining to her before she started chemotherapy that she might develop chronic neuropathy and certainly does not recall anyone explaining that neuropathy can be permanent and disabling. She does recall her oncologist telling her that without chemotherapy, she had a 60%–70% chance of recurrence and that there was a fairly new chemotherapy drug, called oxaliplatin, available for adjuvant treatment of colorectal cancer that was easy to tolerate with few expected side effects. That information, along with her desire to beat the cancer, prompted her to proceed with chemotherapy. After several chemotherapy treatments, another oncologist told her that the chemotherapy would only increase her chances of survival by 8%. She wishes she had stopped then. She now realizes that survival and risk of recurrence are different and that the statistics are derived using different methods.

Sue has undergone extensive neurologic and balance testing and a neurologist confirmed that she has acquired distal symmetrical large fiber predominantly axonal peripheral neuropathy, likely caused by oxaliplatin. She has seen numerous health care providers seeking relief from her neuropathy but thus far, no real relief has been found. Among a long list of treatments she has tried for neuropathy are: pregabalin, duloxetine, chiropractic medicine, acupuncture, electrical stimulation, medical massage, reflexology, ultrasound therapy, monochromatic infrared light energy, pilates, yoga, walking, and tai chi. She has attended support groups and actively seeks clinical trials that might be appropriate. She reads and searches the Internet extensively, searching for treatments to relieve her symptoms and feels abandoned and dismissed by her oncology team who are more focused on the results of her lab work and radiologic testing. She worries about being labeled as “a slacker” or “depressed” when she complains to her health care providers about her symptoms. She wonders if her newly diagnosed hypertension, nausea, lack of appetite, and weight loss are somehow related to her neuropathy and no one seems to offer any answers. She has been told that her symptoms are something she is going to have to live with and that there are other people who are in worse condition. After all, she is cancer-free.

Her lab work, colonoscopy, and computed tomography (CT) scans are all negative for signs of malignancy. She is grateful that she is indeed cancer-free but frustrated that her symptoms have continued for this long with little improvement. She describes her experience as a cancer survivor as being “cut loose.” Every aspect of her care is now “piecemeal and a-la-carte” with no one who takes responsibility for management of her symptoms. She feels as if she has “fallen through the cracks in the system.” She spoke to the director of a cancer survivor program from a major university in Florida and was told that they had nothing to offer her outside of the things she was already doing. She did not qualify to participate in one support group for survivors because she had not been out of treatment for 5 years. She does not qualify for many of the clinical studies because they are looking for participants who are currently undergoing chemotherapy.

Now almost 4 years after her colorectal cancer diagnosis, Sue reports that she has fewer really bad days. The profound weakness is no longer constant although she does feel weak, shaky, and dizzy most of the time and continues to have frequent nausea. Numbness, pain, and cramping in the upper and lower extremities have become progressively more severe but she is learning to cope with her neuropathy and live with her physical limitations. She finds that swimming and regular weight bearing exercise do seem to provide some relief of the neuropathic symptoms in her feet and legs.

Discussion

I met Sue in March 2010 at a peripheral neuropathy seminar, where I was speaking about chemotherapy-induced peripheral neuropathy in patients with colon cancer treated with oxaliplatin. She came to the seminar desperately seeking an explanation for the chronic neuropathy that she had had for well over 3 years. After hearing about how chemotherapy-induced peripheral neuropathy can affect all aspects of physical and emotional well-being, she contacted me by e-mail and shared the extensive records that she has taken since prior to her cancer diagnosis including both her medical history and her reflections on her experience. Her motivation in sharing her experiences was to help educate health care providers about what the experience of chronic peripheral neuropathy is like in the hopes that as a group we will see the urgency in helping patients like her cope with the devastating effects that neuropathy can have on every aspect of a person's life.

Importance of Oxaliplatin in Treatment of Colorectal Cancer

Like Sue, most patients who are diagnosed with stage IIIA, IIIB, or IV colon cancer will receive a chemotherapy regimen that contains oxaliplatin. The Food and Drug Administration (FDA) approved oxaliplatin in late 2002 for palliative treatment of recurrent, metastatic colon cancer and in 2004 for adjuvant treatment of stage III colon cancer. ¹ Undoubtedly, the FDA approval of oxaliplatin was one of the most important breakthroughs in the treatment of colorectal cancer. For oncologists, oxaliplatin is an important tool in their arsenal against a cancer that kills approximately 50,000 Americans each year. ² Remarkably, the most recent statistics indicate a 5-year survival rate for stage III colorectal cancer of approximately 83%. ³ Those of us working in oncology who remember the days before oxaliplatin, lament the lives that may have been saved or prolonged had oxaliplatin been available before 2002.

Incidence of Neuropathy

Despite the clinical benefits of oxaliplatin-based chemotherapy for treatment of colorectal cancer, 30%–72% of patients experience acute, transient, cold-induced neurotoxicity for up to 14 days following each treatment, 48%–76% of patients experience chronic, progressive, primarily sensory, peripheral neuropathy that usually resolves by 18 months after treatment.^4,5 The first evidence that chronic neuropathy may develop after cessation of oxaliplatin was presented in 2006, when a group of oncologists and a neurologist from California published the case of a gentleman who had no symptoms of chronic neuropathy during chemotherapy. He developed neuropathy 2–3 weeks after his twelfth and final chemotherapy, including numbness and tingling in the hands and feet, trouble buttoning his shirt, balance trouble with associated falls, and neuropathic pain for the next 7.5 months. ⁶ Also in 2006, a group of researchers from Italy identified objective evidence of peripheral neuropathy in a group of five colorectal cancer patients who had received their last treatment with oxaliplatin nearly 5 years earlier. It is likely that as more people are treated with oxaliplatin and surviving, that neuropathy will be a major survivorship issue that requires the attention of oncologists, neurologists, primary care practitioners, oncology nurses, physical therapists, and researchers.

Effects on Quality of Life

The long-term effects of peripheral neuropathy caused by oxaliplatin on quality of life have not been adequately described in the literature. Persons with peripheral neuropathy can experience a combination painful and painless symptoms including numbness, allodynia, hyperalgesia, and ataxia. ⁷ Treatments of neuropathy must be guided by a patient's symptoms instead of by a single treatment approach. ⁸ In clinical practice, the majority of treatments utilized have demonstrated efficacy in people with diabetes or other populations with neuropathy but no clear evidence exists to support the use of any of these treatments for chemotherapy-induced peripheral neuropathy. ⁹ While painful symptoms can be treated with neuropathic medications such as anticonvulsants or antidepressants, a pharmaceutical approach is of limited benefit in the treatment of loss of sensation (numbness) or ataxia associated with neuropathy. Physical therapy, gait and balance training, and patient education on maintaining a safe environment may be helpful in enhancement of physical performance and avoidance of injury. ¹⁰

Implications for Research and Education

Prevention and management of chemotherapy induced peripheral neuropathy should be a major goal of symptom management research. With a growing population of colorectal cancer survivors who have received oxaliplatin, peripheral neuropathies represent a major threat to quality of life for cancer survivors. Symptom management, in addition to cancer treatment needs to be a main focus of oncology care. Chemotherapy-induced neuropathy need not be viewed as a “price to pay” for surviving cancer. More efforts must go into educating health care professionals as well as patients about the potential long-term side effects of oxaliplatin and other neurotoxic chemotherapies. Evidence-based methods of preventing and treating oxaliplatin-induced peripheral neuropathies need to be identified and tested. Randomized controlled trials are needed to provide evidence that the treatments adapted from research in non-oncology populations are actually effective for treatment of chemotherapy induced peripheral neuropathy. These are responsibilities that we as health care professionals have to Sue as well as to the other 150,000 Americans diagnosed with colorectal cancer each year.