ASCO 2008 report from freelance medical journalist Stephen Pinn

The 44^th annual meeting of the American Society for Clinical Oncology (ASCO) has just taken place in Chicago. Quite simply it is the biggest cancer meeting in the world. More than 30000 physicians more than 4300 oral and poster presentations. It hosted a massive trade exhibition supported by all the major pharmaceutical companies and a press/media corps of more than 400 journalists writers and broadcasters. A dedicated ASCO follower would probably have walked more than 10 miles over four days traversing the length and breadth of the vast McCormick Place congress centre. Here is the pick of ASCO 2008:

Disease progression can be slowed significantly in patients who have not been given prior chemotherapy for locally-advanced or metastatic breast cancer (BC) by adding a novel targeted therapy (bevacizumab) to a taxane (docetaxel) according to new data presented by Dr David Miles from the Mount Vernon Cancer Centre in Northwood London.

He reported that AVADO (AVAstin in combination with DOcetaxel) was the first phase III trial to evaluate the first-line combination of bevacizumab and docetaxel.

In AVADO 736 previously-untreated women with locally-recurrent or metastatic BC were randomised to receive one of three treatment options: 1) placebo docetaxel 100mg/m² as a control arm 2) bevacizumab 15mg/kg docetaxel or 3) bevacizumab 7.5mg/kg docetaxel all given three times a week.

After a median follow-up of 10.2 months he and his fellow investigators found that patients in the high- and low-dose bevacizumab groups were 28% and 21% less likely respectively to experience disease progression compared to those randomised to docetaxel alone.

A higher rate of tumour shrinkage was documented in the high-dose bevacizumab arm of AVADO than in either the low-dose group or those randomised to docetaxel alone (63.1% 55.2% and 44.4% respectively p=0.0001 and p=0.03 for the high- and low-dose arms vs controls).

Dr Miles emphasised that the safety data were very re-assuring and that patients in both of the bevacizumab arms had only a slightly higher rate of serious adverse events (grade 3 or above): 74.8% for high-dose 74.1% for low dose compared to 67.0% for docetaxel plus placebo.

A new therapeutic approach to the treatment of young men with early-stage testicular tumours has been suggested by new evidence from the first randomised clinical trial to evaluate long-term outcomes in the management of this cancer.

It was revealed that treatment with a single dose of chemotherapy is not only as safe and effective radiotherapy the current standard of care but less toxic.

Professor Tim Oliver from Bart's and The London NHS Trust reported that 1477 patients were randomised to receive a single injection of carboplatin given on an outpatient basis or a course of daily radiotherapy over two or three weeks.

After five years the rate of cancer recurrence was similar in both arms of the study (5% vs 4% for chemotherapy and radiotherapy respectively).

However with a median follow-up of 6.5 years (5 years in 78% of patients) those who received carboplatin were 78% less likely to develop a second contralateral GCT in the remaining testicle (15 patients on radiotherapy vs just two on chemotherapy p=0.03).

A study presented by Dr Hyman Muss from the University of Vermont College of Medicine in the US found that oral chemotherapy with capecitabine does not benefit older women with early-stage breast cancer (ESBC).

This randomised trial included 633 women with ESBC (age 65 years or older) who had already had surgery to remove their tumours. Investigators randomised 326 patients to receive standard chemotherapy and 307 to capecitabine.

It was thought that capecitabine might be just as effective as other chemotherapy agents but easier to tolerate for older patients.

However after a median follow-up of 2.4 years it was found that patients in the capecitabine arm were 2.4 times more likely to suffer a relapse and 2.1 tomes more likely to die than those receiving standard treatment.

Data presented by Dr Gary Morrow from the University of Rochester School of Medicine New York State US showed that the narcolepsy drug modafinil improves cancer-related fatigue.

This randomised study included 642 cancer patients who were undergoing chemotherapy for a variety of cancer types. Investigators found that  patients who had the most severe fatigue benefited the most. Modafinil also had a significantly beneficial effect on sleeplessness but not on depression.

Researchers reported that celecoxib appears to decrease expression of Ki-67 a protein associated with cell proliferation in current and former smokers suggesting that it might potentially serve as a chemoprotective agent for lung cancer.

It had been thought that celecoxib a COX-2 inhibitor increases the risk of cardiovascular disease but no cardiac problems were observed in this particular study.

Reporting these data from 212 current or former smokers Dr Edward Kim from the M.D. Anderson Cancer Centre in Houston Texas US said that Ki-67 expression was significantly decreased with high-dose celecoxib (400mg twice-daily) - but not in those randomised to placebo or to a lower dose (200mg twice daily) of the COX-2 inhibitor.

New imaging techniques have the potential to spare many lung cancer patients from the invasive surgery that will not improve their prognosis according to research presented by Dr Donna Maziak  from the University of Ottawa Ontario Canada.

This study found that positron emission/computed tomography (PET/CT) combined with cranial imaging more accurately identifies disease stage in non-small cell lung cancer (NSCLC) than conventional imaging.

An investigation of 337 patients with newly-diagnosed NSCLC found that twice as many patients randomised to PET/CT were upstaged compared to conventional imaging (14% vs 7%) - meaning that staging was more advanced than previously thought making surgery inappropriate.

A multi-centre randomised phase III trial demonstrated the first evidence of a survival advantage for second-line treatment of advanced transitional cell carcinoma of the ruthenium.

A combination of vinflumine and best supportive care led to significantly longer overall survival (6.9 months vs 4.3 months p=0.04) than best supportive care alone. The addition of the new microtubule inhibitor also led to significant benefits in response rates and progression-free survival.

Three additional years of follow-up in 1867 patients recruited to the International Adjuvant Lung Cancer Trial confirmed the efficacy of  cisplatin-based chemotherapy for completely resected NSCLC for the first five years after surgery.

However there were significant differences between overall survival (p=0.006) and disease-free survival (p=0.04) before and after five years and researchers said that these data suggest the possibility of excess late adjuvant chemotherapy-related mortality.

A delayed positive effect of chemotherapy after radiotherapy for adult patients with low-grade glioma (central nervous system tumours) was reported by investigators from the Radiation Therapy Oncology Group.

Beyond two year progression-free survival and overall survival curves separated significantly (p=0.03) with a reduced risk of death of 48% and progression by 55% for patients treated with both radiotherapy and chemotherapy (procarbazine lomustine and vincristine) compared to radiotherapy alone.

Other highlights included:

• More than one-third of women with breast cancer have deficient levels of vitamin D at the time of diagnosis. They are more likely to experience metastatic tumour spread and more likely to die.
• The number of mastectomies performed at a leading US cancer centre increased 13% in just 3 years among women with early-stage breast cancer. Women who received breast magnetic resonance imaging (MRI) before surgery were more likely to undergo mastectomy than those who did not.
• A major study of more than 14000 survivors of childhood cancers found that they are 5-10 times more likely than their siblings to develop cardiovascular disease in early adulthood.
• Giving combination chemotherapy every two weeks is more effective  than every week in young patients with Ewing's sarcoma and does not increase the side-effect burden.
• A set of 15 genes may predict the degree of aggression of early non-small cell lung cancers (NSCLC) and identify those patients who might benefit most from chemotherapy.