BOWEL CANCER:MEDICINE’S CINDERELLA DISEASE

A special report on the failure of conventional treatment, the latest dietary prevention programmes and the most successful alternative treatments for bowel cancer, the second greatest cancer killer of all.

It’s a disease that isn’t often in the headlines, but bowel cancer is the second biggest cancer killer in the developed world. One in 20 of us will get it. And contrary to popular belief, women are as likely to get the disease as men. In fact, colon ranks second only to breast cancer as the most frequent cause of cancer in women. It’s also the most common cancer in men who do not smoke.

Nevertheless, despite the fact that it’s so widespread, colorectal cancer, as it’s more properly known, has tended to be a medical Cinderella. While the pharmaceutical companies have been falling over themselves to find “cures” for breast cancer, for example, little attention has been paid to the colon. As a result, conventional medicine’s cure rates have been self confessedly disappointing, particularly in advanced cases of the disease. So it’s hardly surprising that patients have increasingly been voting with their feet (and cheque books) by seeking help from alternative practitioners.

Medical solutions

In the US, where the battle lines between alternative and conventional therapies have tended to be most sharply drawn, cancer specialists have done their best to convince patients of the benefits of chemotherapy.

They point to seemingly impressive “response rates”, not bothering to mention that these rarely translate into significant improvements in survival time or quality of life. And yet patients sometimes appear to have been pressured into accepting chemotherapy, even when the oncologist has known that it has little or no benefit.

A peculiarly candid admission of this practice came in 1978 from a leading US specialist in colon cancer, Dr Charles Moertel of the prestigious Mayo Clinic in Baltimore. “Even when administered in most ideal regimens,” he wrote, summarising the value of 5-FU, the major chemotherapeutic drug for colon cancer, “5-FU will produce an objective response in only about 15 to 20 per cent of treated patients. These responses are usually only partial and very transient. This minor gain for a small minority of patients is probably more than counterbalanced by the deleterious influence of toxicity for other patients and by the cost and inconvenience experienced by all patients.”

However, after acknowledging that there was no medical justification for prescribing chemotherapy, Moertel concluded with a statement that sums up the view of medicine toward conventional cancer therapies, to wit: we know it doesn’t work but it’s better than alternative medicine: “This does not imply that (chemotherapy) should be abandoned. Patients with advanced gastrointestinal cancer and their families have a compelling need for a basis of hope. If such hope is not offered, they will quickly seek it from the hands of quacks and charlatans” (New Eng J Med, 1978; 299: 1049-52).

Today, however, conventional medicine is beginning to feel it has something more substantial to crow about in its colon cancer treatments. “Cancer of the colon is a highly treatable and often curable disease,” boasts a recent US National Cancer Institute report. “Surgery is the primary treatment and results in cure in approximately 50 per cent of patients.”

This crude figure is not, of course, quite what it appears, for “cure” in conventional medical parlance means survival for five years. In fact, colon cancers are rarely “cured” because there is a very high recurrence rate, hence the need for repeated surgical interventions. Most patients who contract colon cancer and submit to conventional medical treatment will ultimately die of the disease.

There’s also growing concern among doctors that some surgical techniques may themselves hasten the advance of the disease. It’s now realised that tumours can remain quietly subclinical that is, not yet showing any symptoms but can begin to grow after surgery as a result of the immunodepressive effects of the operation (Ann Chir, 1998; 52: 413-20). There’s also evidence that tumour cells may be released into the body during surgery, causing later metastases tumours which develop from cancer cells that spread through the body (Ann Surg Oncol, 1998; 5: 390-8). In particular, the new technique of laparoscopy has been called into question (Dis Colon Rectum, 1998; 41: 971-8). During laparoscopy, the endoscope is inserted into a small incision made in the wall of the abdomen, which runs a risk of cancer cell “spillage”, potentially spreading the cancer.

Small wonder that a team of British oncologists traditionally less bullish than their American counterparts recently observed: “Despite advancement in surgical and anaesthetic techniques, there has been little reduction in mortality and morbidity from [colorectal cancer] over the past 25 years” (Eur J Surg Oncol, 1998; 24: 477-86).

The major problem with colorectal cancer is that, with or without surgery, the disease often spreads into other areas of the body, particularly the liver, lung and brain, where surgeons have a poor track record. So preventing metastases by chemotherapy has been the primary goal of oncologists.

Shortly after chemotherapy was invented 50 years ago, the toxic chemical fluorinated pyrimidine was developed into a drug called 5-fluorouracil (5-FU for short). Although 5-FU was increasingly used from 1953 onwards, for the first 35 years doctors were disappointed to find that although it might reduce tumour size, it had marginal effects on patient survival. Latterly, however, 5-FU has been combined with other cytotoxic drugs, and these cocktails are now widely prescribed for advanced cases of the disease following surgery.

Extraordinary claims are being made about them, with some doctors claiming a reduction in mortality as high as 33 per cent. But the surgeons are less flattering; some of their own studies show little benefit from the new chemical cocktails and even increases in mortality after their use (Am Surg, 1996; 62: 546-50).

A group of Canadian doctors recently reviewed the entire issue of chemotherapy from an angle relatively new to medicine: the value of therapy in terms of the patient’s quality of life.

Quoting a review of a number of studies which showed that chemotherapy increases five year survival from colorectal cancer by an average of 7 per cent, they boldly stated: “Despite the US National Institutes of Health consensus statement endorsing chemotherapy, many clinicians regard such a seemingly small benefit not worth the expense, inconvenience, discomfort and risk of treatment for their individual patient with colorectal carcinoma” (Ann Chir, 1998; 52: 711-5).

Adding to the uncertainty of chemotherapy are its side effects. These are, of course, substantial since the treatment destroys healthy cells as well as cancerous ones. A recent study has shown a litany of side effects for patients whose immune systems are already compromised by the cancer. These range from nausea, vomiting and diarrhoea to thrombocytopenia (too few platelets), leukopenia (decrease in number of leukocytes) and neutropenia (decrease in number of neutrophils) (J Clin Oncol, 1998; 16: 3537-41).

These latter three are caused by the destruction of the white blood cells that normally fight infections, and they can often result in major problems; if accompanied by a fever, death will ensue within hours or even minutes. Indeed, many cancer patients may have actually been killed by chemotherapy, and not the disease (J Clin Oncol, 1997; 15: 3320-9).

A new chemotherapy drug called irinotecan (marketed by Upjohn as Camptosar) has recently come into use, intended for patients who don’t respond to 5-FU. However, studies show that, like 5-FU, Camptosar’s benefits are limited, extending survival by about three months compared to no treatment at all but with all the attendant side effects (Lancet, 1998; 352: 1413-8). Chemotherapy has also been found to be useless in treating metastases in the liver the most common result of colon cancer (Arch Med Res, 1998; 29: 319-24).

Gene therapy, although heavily trumpeted in the media, is in reality a distant hope, as oncologists will admit among themselves.

First stage trials are currently underway in animals, but already concerns are being raised over toxicity, side effects and lack of ability to target specific tumours (Hematol Oncol Clin North Am, 1998; 12: 595-615).

Screening tests

Because of such poor outlooks for colorectal cancer patients, the official line is that people should be encouraged to have regular check ups to detect the cancer before it takes hold, particularly those individuals who are at high risk (see box, p 1). However, in practice there are many problems in carrying through this advice. First, the warning signs of the cancer (iron deficiency anaemia, rectal bleeding, change in bowel movements, abdominal pain and weight loss) tend to become noticeable only when the cancer is already well established.

Second, the diagnostic tests themselves are sometimes not reliable. The simplest test, called the occult blood test, measures blood in the faeces but is notoriously prone to false positive results and, more importantly, false negatives. The more complex barium enema fares little better.

The more reliable tests, such as sigmoidoscopy and colonoscopy (visualisation of different areas of the colon with a lighted tube inserted in the anus) are invasive, discouraging patients from undergoing routine checks. Further more, experience has also shown that even these sometimes fail to detect pre cancerous polyps (Ann R Coll Surg Eng, 1998; 80: 246-8). Finally, if all patients who were at risk were to demand routine check ups, neither private nor state run systems would be able to cope. But as the US National Cancer Institute admits, “limiting screening or early cancer detection to only high risk groups would miss the majority of colorectal cancers” (PDQ Statement, June 1999).

Prevention

For many oncologists, the major hope for the future of colon cancer lies in prevention. Some see a bright prospect for drugs as preventive agents after it was unexpectedly observed that aspirin, which is a non steroidal anti inflammatory drug (NSAID), reduced the incidence of colorectal cancer. A major clinical trial is currently underway in Europe, testing daily aspirin doses as high as 350 mg among patients who have undergone surgery to remove benign colorectal polyps.

An epidemiological study has also been completed on other NSAIDs. In 100,000 Americans aged over 65 who had been taking NSAIDs for conditions like arthritis, two year usage of the drugs reduced colon cancer risk by nearly 50 per cent, and one year usage, by about 40 per cent (Arch Intern Med, 1999; 159: 161-6). The authors predict similar results will be found with aspirin.

However, rationalising that aspirin offers unwanted side effects (such as irritation to the stomach lining), drug manufacturers are now marketing NSAIDs, such as sulindac and indomethacin, as primary cancer preventatives. But a recent review article reported that “their effects are incomplete and may cause severe toxicity” (Nippon Geka Gakkai Zasshi, 1998; 99: 385-90).

The much larger hope for prevention is in the area of diet and lifestyle (see box below). In the last 20 years, there has been a major shift in attitude by the medical profession towards the idea that environmental factors, and in particular diet, are among the major causes of all cancers. In fact, bowel cancer was the first cancer to be linked specifically to diet after observations by Dr Denis Burkitt in the 1950s suggested a high fibre diet prevented the disease. At first, Burkitt was ridiculed, but the epidemiological evidence concerning the role of diet soon became overwhelming.

Particularly striking was the observation that the Japanese and Chinese have 20 times less colon cancer than Americans, but when they immigrate to the US and start eating more animal fats and protein but less fibre, their rate of colon cancer rises to the national level within a generation. To date, there have been literally thousands of studies exploring the role of diet in colorectal cancer, leading to widespread agreement that dietary factors are the primary cause, accounting for as much as 90 per cent of its incidence (see box below) (Eur J Cancer Prev, 1998; 7: S79-80).

!ATony Edwards

Alternative treatments, continued on pg 10