American Society of Clinical Oncology (ASCO).

This year's ASCO Gastrointestinal Cancers Symposium was held in San Francisco (15-17 January 2009) and continues to be a vitally important meeting for the presentation of high-quality translational research across the spectrum of gastrointestinal malignancy where all aspects of cancer management were addressed. We highlight four presentations of note.

Rectal cancer patients are getting younger

A paper highlighting a new demographic trend in rectal cancer studies was presented by Joshua Meyer Weill Cornell Medical College, New York; Abstract 315) [1]. He reported a 2% rise in the annual incidence of rectal cancer in patients below the age of 40. This finding was in direct contrast to the findings of the same study with respect to older patients, where the incidence of, for example, non-rectal colon cancer had actually decreased by 0.2% per annum (no difference was identified when gender and ethnicity were used as discriminators). Single institution data revealed that between 1990 and 1994, 2% of all patients with rectal cancer were under 40. This is in comparison to the period between 2002 and 2006 when 7% of patients with rectal cancer were found to be in the under-forty age group.

This initial observation by the clinicians at Weill Cornell was then verified when the researchers went on to corroborate their findings with the NCI (National Cancer Institute) Surveillance, Epidemiology, End Results (SEER) database for rectal cancer for all cases between 1973 and 2003. The study was limited to carcinoma of the rectum/rectosigmoid, and analysis was also made of sigmoid colon, descending colon and colon excluding the rectum'.

The analysis demonstrated an annual increase of 2.6% in the incidence of rectal cancer and of 0.2% P<0.0001) in the incidence of cancer of the rectosigmoid. Interestingly, the annual percentage change for total colon cancer averaged -0.2%, which included an increase of 0.4% per annum for sigmoid cancer and a statistically significant decrease for cancer of the descending colon.

Dr Meyer concluded that extensive analysis, applying genetic, clinical, demographic and/or lifestyle factors, seemed to have no statistical impact on these findings: he and his colleagues were unable to account for the increased incidence in the younger age group. Further studies are now under way, and there is a need to raise awareness of this issue in younger patients.

Radiation-loaded beads show promise for colorectal liver metastases

Unresectable colorectal hepatic metastases that are refractory to chemotherapy are known to have survival rates of approximately 4-5 months. An approach to their treatment, as seen in limited retrospective studies, using locally delivered radiation with 90Yttrium resin microspheres has shown activity against them.

Maurizio Cosimelli (Regina Eleni Cancer Institute, Rome; Abstract 452), presented his Phase II multicentre study on behalf of the Italian Society of Integrated Locoregional Therapies in Oncology (SITILO) [2].

In this study 52 patients were enrolled, of whom 50 were eligible. Of these eligible patients, 60% had more than four hepatic metastases (median diameter 50 mm, range 8-120 mm) involving 25-50% of the liver parenchyma. Over 75% of these patients had already received more than three chemotherapy regimens. The technique of introducing these radioactive spheres first involves embolisation of the gastroduodenal and right gastric arteries and is followed by a single injection of the treatment into the hepatic artery by arteriography, delivering 1.7 GBq per sphere. The response to treatment was taken to be a reduction in the maximum diameter of the metastases to at least 35 mm. Of the 46 evaluable patients, one had a complete response, 11 a partial response, 12 stable disease and 22 progressive disease. In addition, two patients were sufficiently downstaged to enable planning of radical resection of three or more segments. The time taken to respond was an average of 6 weeks. Grade 1 or 2 adverse events, mostly fever and pain, were reported by eight patients earlier than 48 hours after treatment and by 11 later than 48 hours.

Patients' survival had increased from the 4-5-month expectancy, to 8 months for non-responders, and to 16 months for responders. 'These results justify Phase III studies to investigate earlier use of this treatment and its use in combination with chemotherapy,' said Dr Cosimelli.

Mutation testing in metastatic CRC could save millions

Studies have shown that the anti-epidermal growth factor receptor monoclonal antibody drug cetuximab (Erbitux) has activity only against wild-type KRAS tumours (i.e. tumours without mutations). KRAS mutations are estimated to occur in 35.6% of cases of metastatic colorectal cancer and Veena Shankaran (Northwestern University of Chicago, USA; Abstract 298) [3] proposed that the healthcare system would be saved a great deal of money if patients with KRAS mutations were not treated with this drug. Based on the 2008 American Cancer Society estimated annual incidence of metastatic CRC of 29,762 new metastatic CRC cases, initial KRAS testing by PCR would cost $13 million ($452/patient). The cost of cetuximab treatment was estimated $71,120 per patient. By withholding the drug from patients with KRAS mutation, a potential saving on treatment costs of $740 million could be made. If the costs of visits to clinics, infusions, and toxicity management are considered, this saving could be even greater. Dr Shankaran expects to refine these costings in the future. Although cetuximab is used more commonly in second- and third-line therapy where treatment duration is shorter, KRAS-based treatment selection is likely to result in cost savings across all lines of therapy. In addition, development of validated predictive molecular markers would not only spare patients ineffective and toxic therapies, but would also greatly reduce futile costs.

Novel drug delivery system improves pancreatic cancer survival

The promising results of a Phase II study for patients with unresectable locally advanced or metastatic pancreatic cancer were reported by Dr Michael Lohr (Karolinska Institute, Stockholm, Sweden; Abstract LBA120) [4].

The multinational study supported by MediGene AG, involved 200 patients randomised to receive either gemcitabine alone, or gemcitabine with paclitaxel. EndoTAG-1, which employs a positively charged lipid complex, delivered the paclitaxel to the negatively charged endothelial surface, thereby directly inhibiting angiogenesis of the tumour. Patients received 11, 22, or 44 mg/m2 paclitaxel in the trial. All patients underwent a 7-week cycle of treatment, however, if a favourable response was seen with EndoTAG-1, more cycles were given.

Thirteen patients who received 11 mg underwent four cycles, eight patients receiving 22 mg underwent eight cycles, and seven patients receiving 44 mg underwent five cycles. There was no evidence of disease progression in 43% of the gemcitabine group, and 53-69% of the combination therapy group after the first cycle of treatment. The progression-free survival was 2.7 months in the gemcitabine group, vs. 4.1-4.6 months in the combination group. The median overall survival was 7.2 months in the gemcitabine arm, and 8.4-9.4 months in the combination arm. The median 6-month survival was 63% with gemcitabine and 67-80% with combination treatment, whereas the 12-month survival with gemcitabine was 17%, and with combination treatment was 22-36%.

There were no cases of cumulative toxicity, and the few complications were manageable infusion-related reactions that were dose dependent. There were no reported cases of neurotoxicity, pulmonary or cardiovascular toxicity, or any alopecia. There was, however an increased incidence of thrombocytopenia with increased dosage.

Conclusion

This meeting generated a wealth of data from which only selected presentations are highlighted here. Comprehensive coverage of the meeting including abstracts in full is available at www.asco.org

References

All abstracts were presented at the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium, San Francisco, 15-17 January 2009.

[1.] Meyer JE, Sherr DL, Schnoll-Sussman FH et al. Incidence of rectal cancer in patients under age 40: an analysis of the SEER database. Abstr. 315.

[2.] Cosimelli M, Mancini R, Carpanese L et al. Phase II multicenter study of 90Yttrium resin microspheres for patients with unresectable colorectal liver metastases who had failed prior oxaliplatin- and irinotecan-based regimens. Abstr. 452.

[3.] Shankaran V, Bentrem DJ, Mulcahy MF et al. Economic implications of KRAS testing in metastatic colorectal cancer (MCRC). Abstr. 298.

[4.] Lohr M, Haas S, Bechstein W et al. A phase II trial of cationic liposomal paclitaxel in combination with gemcitabine in patients with unresectable pancreatic cancer. Abstr. LBA120.

Correspondence to: Rachel Aguilo (email: [e-mail])

Rachel Aguilo and Sascha Dua

Royal Free Hospital, London, UK