When less is more

The conventional approach to chemotherapy treatment for cancer is to give the patient a cocktail of different chemo drugs at the maximum tolerated dose (MTD). The idea of MTD treatment is to hit the cancer with the most toxic treatment the patient can stand in the hope that it causes the maximum damage to the disease. Normally a treatment consists of a number of cycles of chemo using a mix of drugs, with the idea that each drug will attack the tumour in a different way – reducing the chance of the tumour surviving the onslaught. And it’s an onslaught for the person receiving the treatment too – most chemotherapy drugs are toxic to a wide range of cells, not just cancer cells. Hence the hair loss, the nausea, the immune suppression, fatigue and the rest of the side effects that makes chemo so hard.

Of necessity a person needs recovery time after each cycle of chemotherapy. Blood counts need to recover, sickness needs to pass, people need to regain some strength. Unfortunately that’s recovery time that tumours can also use to recover. The highest rates of tumour kill tend to be at the least cycles, the later cycles tend to be less effective, particularly if resistance starts to kick in.

However, this isn't the only way of delivering treatment. An alternative approach to chemotherapy has been developing for some time. Low dose metronomic chemotherapy involves many of the same drugs as MTD chemo, but delivered at low doses, often in tablet form, but with no treatment breaks. The continuous dosing is possible because at these low doses the drugs work in very different ways to when they are delivered at MTD levels. The side effects are minimal as the drugs are no longer acting as potent toxins to massively kill cells.

Instead of acting as cytotoxic agents, these drugs – including cyclophosphamide, capecitabine, etoposide, methotrexate, vinorelbine and temozolomide – act on the aspects of the life support systems that tumours depend on for survival. They act on the blood supply the tumours depend on for nutrients. Some of these drugs also act on the immune system, working to make the tumours more visible to the immune cells that fight cancer.

It’s a very different approach to cancer treatment and it has been used now for more than thirty years. It has been through multiple clinical trials in a wide range of cancer types, including breast, prostate, lung and other cancers. Most of these trials are in later stage cancers, when standard therapies have failed rather than in newly diagnosed disease. The results are generally good and in these late stage patients the responses can be extremely positive and often far in excess of high dose chemo when used at the same stage of disease.

All of which has to beg the question – after all these years and with all of this evidence, why are so many oncologists still prescribing high dose chemo to late stage cancer patients? Why are they treating patients with the highest possible doses when there is an alternative that is gentler and has strong levels of evidence in its favour? Why is it that metronomic chemotherapy is still viewed as some outlandish, experimental and dangerous treatment when it’s the last ditch high dose chemo that causes the toxicity and destruction of the quality of life for patients with no curative treatments left?