Starving the body of food for a couple of days could help in the fight against cancer, according to new research.

Scientists have discovered that a 48-hour fast seems to protect the body’s healthy cells against the toxic effects of chemotherapy drugs.

The breakthrough could provide a solution to a problem that has confounded cancer experts for years – how to target chemotherapy so it destroys cancer cells but leaves healthy ones intact.

It seems depriving healthy cells of the food they need for fuel sends them into a kind of survival mode, where they become highly resistant to stress or damage.

Experts describe this behaviour as similar to animals waiting out winter food shortages by hibernating.

But cancer cells do not react in the same way. Instead, they carry on growing and remain just as susceptible to the effects of chemotherapy as they do when the body has a full supply of food.

The result could be that doctors can cure more cancers by using higher doses of chemotherapy drugs to shrink or destroy tumours.

Cancer affects one in three people in the UK at some point in their lives.

Many end up needing a course of chemotherapy to try to control the spread of the disease.

Treatment may involve drugs which block the effects of certain hormones or affect the immune system, but the main group of drugs that are used are called cytotoxics, which mean they poison cells to stop them reproducing.

There are more than 100 different cytotoxic drugs in use for cancer, but none is capable of telling the difference between normal cells and cancer cells.

Although healthy cells usually recover from the toxic effects of the drugs, they need some time to recuperate.

This means treatment is often given in short bursts, with several weeks’ break in between to allow normal cells a chance to recover. But many patients still end up suffering unpleasant side-effects such as hair loss, nausea and extreme tiredness.

If doctors could find a way of protecting healthy cells, they could give patients shorter but more intense bouts of treatment, with far fewer adverse effects.

For nearly 50 years, there has been evidence that fasting – or limiting calorie intake – can slow the ageing process by switching on some kind of internal protection mechanism in the body.

There is even a Calorie Restriction Society, a U.S-based organisation whose members deliberately limit food intake in an attempt to live longer.

The latest findings, published in the Proceedings of the National Academy of Sciences, suggest that depriving the body of calories in this way could also transform cancer care.

For the study, mice with cancer were starved for two days before being given a high dose of chemotherapy.

Tumour cells were destroyed by the drugs, but the healthy cells survived the treatment intact.

In a separate group of mice that ate normally, the treatment killed more than half of them and caused severe weight and energy loss in the survivors.

Laboratory tests suggested fasting had a similarly beneficial effect on human cells. But UK cancer experts have warned patients not to starve themselves until there is more evidence that it works and is safe.

Cancer Research UK science information officer Henry Scowcroft said: “This is an interesting result based on solid science and may open up new avenues to improve cancer treatment.

“But it doesn’t really fit with what we know about chemotherapy, which is that if you are healthy, well-fed and you get enough nutrients you tend to cope with it better.

“Until these findings are confirmed in human trials, we strongly advise people undergoing cancer treatment to eat a healthy, balanced diet.”

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Chemotherapy given both before and after surgery to remove liver metastases (secondary cancers) improves progression free survival over surgery alone in patients with metastatic colorectal cancer, concludes a study published recently in The Lancet. The phase III European Organization for Research and Treatment of Cancer (EORTC) study demonstrated that perioperative chemotherapy (i.e. that given before and after surgery) was compatible with major liver surgery.

Liver metastases are found in 40 to 50% of the nearly one million people diagnosed in the world each year with colorectal cancer. Despite advances in chemotherapy five year survival for metastatic colorectal cancer is less than 5%. In the subset of patients where surgery to remove liver metastases (resection) is possible, five year survival increases to 60 %. Recurrence after surgery in this group, however, is common. It has been suggested that the combination of chemotherapy and surgery can reduce the risk of relapse. The rationale for this is that preoperative chemotherapy allows surgery to be undertaken on tumours that have shrunk in size, while postoperative chemotherapy acts on any cancer cells remaining in the liver.

This multi-centre trial, which was led by Bernard Nordlinger, from the Hôpital Ambroise Paré ( Paris, France), and involved researchers from Europe, Australia and Hong Kong, set out to investigate whether combining perioperative chemotherapy with surgery could reduce the risk of relapse compared to surgery alone. The collaboration represents one of the few studies to have investigated combining chemotherapy with surgery in such patients, and is the first to assess the benefits of preoperative chemotherapy.

In the trial, 364 patients, with histologically proven colorectal cancer and up to four operable liver metastases, were randomised to receive surgery alone (n=182) or surgery plus the FOLFOX4 chemotherapy regimen with six cycles before and six cycles after (n=182). The FOLFOX4 regimen consisted of calcium folinate (leucovorin), followed by bolus injection of 5-fluorouracil and a 22 hour infusion of 5-fluorouracil on days one and two, and oxaliplatin on day one. Patients were recruited from 78 hospitals in 11 countries.

Upon further evaluation, 11 patients in each arm were found to be ineligible for inclusion so that in total 152 patients in the surgery alone group and 151 in the chemotherapy and surgery group underwent liver surgery.

In an intention to treat analysis results show that progression free survival does not differ significantly between the two groups (P=0.058 versus the required P=0.0434). However a second analysis, just including the patients who were able to undergo surgery, shows that the progression free survival at three years was 33.2 % in the surgery only group versus 42.4 % in the adjuvant chemotherapy group (HR 0.73, P=.025). This was statistically significant and represents an absolute increase in progression free survival of 9.2 %. Progression free survival is defined as the time until progression, recurrence or death. Overall survival is still being monitored.

The most common adverse events seen with preoperative chemotherapy included neutropenia, diarrhoea, stomatitis/pharyngitis and neurological toxicities. Similar side effects were seen following postoperative chemotherapy with the exception of stomatitis/pharyngitis. Reversible post operative complications (such as biliary fistula, hepatic failure, wound infection and urinary infection) occurred more frequently in patients who had received chemotherapy than the surgery only group (25 % versus 16%, p=0.04).

“We conclude that perioperative FOLFOX4 chemotherapy reduced the risk of events of progression free survival by a quarter and was compatible with major surgery,” writes Nordlinger and colleagues, adding that although the trial was restricted to patients with four or fewer metastases, the conclusions are likely to be valid for those at higher risk. Future trials, they add, should look at more intense chemotherapy or combinations with targeted agents.

In an accompanying editorial Scott Kopetz and Jean-Nicolas Vauthey, (University of Texas MD Andersen Cancer Centre, Houston, TX),write: “Despite the modest benefits on progression-free survival, this study clearly shows the advantage of preoperative FOLFOX to select the patients most likely to benefit from hepatic resection.”

The study, they add, confirms the importance of multidisciplinary care and the improved outcomes that can be achieved when the best of medical and surgical oncology are integrated.

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Regular monitoring with positron emission tomography (PET) scanning – which detects changes in the function of cells – achieves earlier detection of recurrences of colorectal cancer than conventional scanning that simply looks at the structure of body tissues, a prospective study has shown.

Colorectal cancer – cancer affecting the lower part of the digestive tract – is the second most common cause of cancer-related deaths in Western countries. Most people newly diagnosed with the disease undergo surgery to completely remove their tumour. However, approximately half of people who have curative surgery go on to develop recurrent disease. The median survival after surgery is two years. Adjuvant chemotherapy – anticancer drug treatment given just after surgery – improves the prognosis, but one-third of patients having this treatment still suffer a recurrence within two years after surgery.

Surgery to remove metastases in the liver or lung in people who have a recurrence of colorectal cancer improves survival so that 35-40% are alive after five years. This means that it is very important to follow up patients with colorectal cancer regularly to detect recurrence as early as possible so that tumour tissue can be removed and their chances of survival improved. Most people have regular clinical examinations and computed tomography (CT) scans, which provide detailed images of structures inside the body, to look for signs of recurrence.

French researchers carried out a study to see if functional positron emission tomography (PET) imaging – looking at the function of body cells by measuring their use of a radio-labelled isotope of glucose (18fluorodeoxyglucose, 18FDG) – could detect recurrences of colorectal cancer earlier than CT imaging. They randomly allocated 130 patients who had undergone curative surgery for colorectal cancer followed by chemotherapy to regular follow-up with conventional tests or with PET scans.

All the patients had six follow-up appointments, starting from the ninth month after their initial surgery and continuing to 24 months or their death. They had a physical examination, measurement of biological markers for cancer, an ultrasound scan every three months (replaced by abdominal CT scans after 9 and 15 months) and a chest X-ray every six months. Patients in the PET group also had 18FDG-PET scans after 9 and 15 months.

Results showed that recurrence occurred in 46 patients – 25 in the FDG-PET group and 21 in the group having conventional follow-up. Use of PET scans revealed unexpected tumours in a further three patients.

Recurrences were detected after a significantly shorter time with PET scanning (12.1 months, on average) compared with conventional follow-up (15.4 months, P=0.01). Recurrences in the PET group were also more frequently cured by surgery, with 10 patients with recurrence being cured, compared with only two patients in the group not having PET scans.

Professor Iradj Sobhani, Université Paris 12 et Hôpital Henri Mondor, Paris, France, and lead author of the study, commented: “We showed that FDG-PET is a valuable adjunct to conventional follow-up. Using this new follow-up strategy increased the rate of curative resection by allowing us to detect recurrences of colorectal cancer at an earlier stage.” He added: “Regular FDG-PET monitoring in the follow up of colorectal cancer patients may permit the earlier detection of recurrence. We would expect improved patient survival if such as follow-up programme was undertaken.”

PET scanners have now been developed that can detect smaller tumours than the machine used in the French study. The study authors noted that coupled PET and CT scans appears to provide more accurate diagnoses than using the techniques separately. They predicted that using combined PET-CT scans would make it easier to correctly determine the stage of a patient’s cancer, although more research is needed to confirm this.

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Patients with breast cancer who developed anemia during chemotherapy had nearly three times the risk of local recurrence as those who did not, according to a study published in the April 1 issue of Clinical Cancer Research¸ a journal of the American Association for Cancer Research.

“We speculate that there may be an interaction between chemotherapy/radiotherapy and anemia,” said lead researcher Peter Dubsky, MD, a senior consultant in the department of surgery at the Medical University of Vienna, Austria. “Both treatment modalities have been shown to be less effective in anemic patients. Since we do not see the effect in terms of relapse-free survival, the interaction with local adjuvant treatment may play a more important role.”

Dubsky and his colleagues from the Austrian Breast and Colorectal Cancer Study Group examined data from a randomized, clinical trial comparing adjuvant hormonal treatment and tamoxifen with the standard treatment of cyclophosphamide, methotrexate and 5-fluorouracil (CMF). All women in the trial were premenopausal and had positive estrogen and/or progesterone receptor status. Patients who underwent breast-conserving surgery received mandatory radiation. Radiation was optional in women who underwent modified radical mastectomy.

For the current analysis, the researchers focused on anemia data from the 424 patients in the CMF arm, as the rates of anemia among those who received the hormonal treatment were low. They examined local relapse-free survival, relapse-free survival and overall survival.

Anemia occurred in 18.2 percent of patients who received CMF chemotherapy. Anemia was defined as an incidence of at least one serum hemoglobin level below 12 g/dL during chemotherapy through the first follow-up date three months after adjuvant treatment concluded.

After a median follow-up of 61 months, 39 local relapses occurred: 6.9 percent in patients without anemia and 19.5 percent in patients with anemia. The 5-year rates of relapse were 8.2 percent among nonanemic patients and 19.6 percent among anemic patients. Patients without anemia experienced a significantly longer local relapse-free survival than patients with anemia, according to the study.

Other factors that significantly increased local relapse-free survival were younger age at diagnosis and negative lymph node status. Any relationship between anemia and tumor size, postoperative radiation or type of surgery did not have an effect on local relapse-free survival, researchers say.

Relapse-free survival did not differ significantly with the presence or absence of anemia. “There seemed to be no difference when distant or contralateral events were part of the analysis,” said Dubsky. “The effect was limited to local recurrences. Any explanation of the limit is pure speculation.”

No difference in overall survival was evident, but Dubsky says he doubted one would be seen given the number of patients and the length of follow-up. Follow-up of 10 to 15 years would be needed to observe any significant differences, he says.

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The use of combination chemotherapy following surgery did not improve survival in patients with gastric cancer, according to a randomized clinical trial published online March 11 in the Journal of the National Cancer Institute.
The only potentially curative therapy currently available for non-metastatic gastric cancer is surgery. Recent studies have suggested that a combination of cisplatin, epirubicin, 5-fluorouracil and leucovorin (PELF) improves outcome in patients with metastatic gastric cancer.

To test the PELF combination in patients with localized disease, Francesco Di Costanzo, M.D., of the University Hospital Careggi in Florence, Italy, and colleagues in the Italian Oncology Group for Cancer Research conducted a randomized controlled trial in which 258 patients were treated with surgery or surgery followed by chemotherapy.
With a median follow-up of 72.8 months, there was no significant difference in disease-free survival or overall survival between the two trial arms. Specifically, 47.7 percent of the patients treated with chemotherapy had progressive disease compared with 51.6 percent of patients in the control arm. Overall survival was similar; at the end of the follow-up period, 47 percent of the patients in the chemotherapy were still alive compared with 45.3 percent in the surgery-only arm.
“Our study confirms that a dose-intense regimen like PELF, which showed very promising results in advanced gastric cancer, is not effective in an adjuvant setting,” the authors write. Considering the negative results in this trial and other recent adjuvant chemotherapy trials in gastric cancer, the authors write, “Adjuvant chemotherapy alone remains a controversial approach in operable gastric cancer.”
In an accompanying editorial, Aiwen Wu, M.D., and Jiafu Ji, M.D., of the Beijing Cancer Hospital and Institute in China discuss the conflicting results obtained from recent trials that tested the value of chemotherapy and radiation in localized gastric cancer.
Despite the inconsistency of the overall data, the editorialists conclude that chemotherapy, radiation, or a combination of the two should be used in patients with gastric cancer. “Surgery alone is no longer the standard treatment for patients with resectable gastric cancer, independent of the patient population or the practice location,” they write.

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