News focus:The ‘miracle’ chemo drugs

LUNG CANCER
* EGFR blockers
New so-called ‘breakthrough’ drugs like erlenotib block what are known as ‘epidermal growth-factor receptors’ (EGFR), an important intracellular signalling pathway involved in cancer growth. The spin is that they supposedly kill cancer cells while apparently not harming normal ones. Survival benefit: none. A recent test of erlenotib showed no improvement over 10 and a half months in terms of patient survival compared with a placebo. A recent trial of Iressa (by AstraZeneca), licensed for use in 25 countries, was prematurely shut down after showing no survival benefit, according to the US National Cancer Institute (NCI). Side-effects: skin rashes and diarrhoea sufficient to make people drop out of the study (J Clin Oncol, 2005; 23: 5892-9).

BREAST CANCER
* Anthracyclines
This is given instead of the chemo cocktails based on 5-FU. Survival benefit: six months’ worth reduces death rates by 20 per cent in older women, and almost 40 per cent in those under 50 (Lancet, 2005; 365: 1687-717). But note: survival statistics are greatly skewed by the fact that nearly 50 per cent of patients are misleadingly diagnosed as ‘ductal carcinoma in situ’ (DCIS), an abnormality that rarely spreads or causes death. Side-effects: increased infections, unusual bleeding or bruising, difficulty swallowing and breathing, chest pain, fever, sore mouth and throat, bloody vomiting and diarrhoea, hair loss and congestive heart failure.

* Taxanes
These are the latest chemo drugs (derived from the yew plant) and attack the microtubules in cancer tumours. Survival benefit: combined with a 5-FU cocktail, resulted in only marginal improvement, with 7 per cent more patients alive after five years. Side-effects: significantly worse than with older chemo protocols with, in particular, febrile neutropenia (loss of white blood cells causing fever) (N Engl J Med, 2005; 352: 2302-13), peripheral nerve damage, vomiting, and muscle and joint pain. Overall advantage as just-in-case treatment (chemo and radiation after surgery): none; and no survival advantage over surgery (JAMA, 1991; 265: 391-5).

PROSTATE CANCER
* Docetaxel (a new taxane)
Survival benefit: two months, when combined with other drugs such as estramustine and prednisone (Urology, 2005; 65 [6 Suppl]: 8-12). It appears to work better with calcitriol, a compound derived from vitamin D, and is currently under investigation (BJU Int, 2005; 96: 508-13). Side-effects: “severe toxicity”, including neutropenia and asthenia (debilitating weakness) (J Chemother, 2005; 17: 242-6).

CANCER OF THE PANCREAS
* Gemcitabine (an antimetabolite)
This mainly works by interfering with a cell’s DNA. Survival benefit: seven months more than surgery alone (which itself offers a seven-month survival) (American Society of Clinical Oncology Annual Meeting, Orlando, Florida, 14 May 2005). Side-effects: fever, spots, skin rash with or without itching, swelling of fingers, feet or lower legs, unusual bleeding and bruising, unusual tiredness or weakness, constipation, diarrhoea, general feeling of illness, loss of appetite, loss of hair, muscle pain, nausea and vomiting, runny nose, sweating, sleep problems and weakness in limbs. Outlook with conventional treatment: only 4 per cent of sufferers are alive five years after diagnosis.

COLON CANCER
* Xeloda
Released in 2001 and hailed as a breakthrough, this drug simply metabolises in the body into fluorouracil (5-FU), the 40-year-old highly toxic backbone of colon-cancer treatment known to have, at best, a “partial and transient” response (N Engl J Med, 1978; 299: 1049-52). Survival benefit: 13 per cent for stage III patients; none for stage II patients. Side-effects: neutropenia (loss of blood white cells), bone-marrow suppression, mouth sores, and blisters and sores on the hands and feet.

* Erbitux (cetuximab)
The first monoclonal antibody for advanced, metastasised (widespread) colon cancer, this intravenous treatment is often given in combination with irinotecan (Camptosar), another anti-cancer drug approved for colorectal cancer, or by itself, if patients cannot tolerate irinotecan (see below). It contains both human and mouse components, and is believed to work by targeting a protein called ‘epidermal growth-factor receptor’ (EGFR), found on the surface of cancer cells, and supposedly interfering with cancer-cell growth. Survival benefit: none, according to the NCI, after four years of follow-up. At best, it delays tumour growth by four months as a combo treatment, and by one and a half months on its own. Side-effects: granulocytopenia (like neutropenia, a low white cell count), paraesthesia (‘pins and needles’), diarrhoea, vomiting and nausea. It can also cause liver damage.

* Irinotecan
This antineoplastic (anti-cancer) drug interferes with the growth of healthy cells as well as cancerous ones. Survival benefit: reduced doses (high doses are toxic) give advanced-cancer patients a further three months – if they survive the drug. Side-effects: so hard on the immune system that one American trial was suspended half-way because of a worrying number of deaths (NCI press release, April 2001).

Tony Edwards