Weight-adjusted Dosing of Dalteparin Prevents VTE in Advanced Pancreatic Cancer

Weight-adjusted dosing of dalteparin, a low-molecular-weight heparin (LMWH), prevented the occurrence of venous thromboembolism (VTE), including lethal VTE, in patients with advanced or metastatic pancreatic cancer, according to results of a multicenter, randomized, phase IIB trial presented at the ECCO 15 — 34th ESMO Joint Conference.

UK FRAGEM is the first study of LMWH in this setting to utilize weight-adjusted dosing at the same dose recommended for secondary prevention in patients who have already experienced a VTE, explained lead author Anthony Maraveyas, MD, Queen’s Hospital Oncology, London, UK. He suggested that LMWH should be used in patients with advanced or metastatic pancreatic cancer, who are at greater risk of VTE than cancer patients with other solid tumors.

“We do not need more data to start using LMWH. The daily injections [of LMWH] may be a small price to pay [in patient discomfort] to avoid the risk of VTE,” Dr Maraveyas told listeners.

VTE is exacerbated by chemotherapy, and can shorten survival. There is presently no standard of care for thromboprophylaxis, he continued. Although none of the previous trials of LMWH in this setting met the primary endpoint, they did not employ weight-adjusted dosing, which appears to be key to the success of this strategy.

The study enrolled 171 patients with histologically confirmed advanced or metastatic pancreatic cancer. Of these, 123 patients were randomized to either gemcitabine 1000 mg/m² or the same dose of gemcitabine plus weight-adjusted dalteparin (12 weeks of subcutaneous injections of 200 IU/kg week 1-4, adjusted to 150 IU/kg week 5-12) for 3 months of treatment. No anticoagulation or vena caval filters were allowed. Previous documented VTE within the previous 6 months was also an exclusion criterion.

The study met its primary endpoint, significant reduction in VTE for dalteparin; VTE occurred in 31% of the gemcitabine-alone arm versus 12% in the dalterparin-containing arm (P <.02). Dalteparin reduced clinical VTE from 24.2% in the gemcitabine arm to 8.5% (P <.038). All types of VTE were reduced by dalteparin within the first 100 days of treatment from 25% in the gemicitabine arm to 3.5% (P <.002), and clinical VTE as well as lethal VTE was virtually abolished by dalteparin (17.7% versus 0, and 9% versus 0 , respectively, in the two arms).

No difference was observed between the two treatment arms for overall survival, time to treatment failure, and response rates. However, patients who sustained a VTE fared worse in terms of survival in either arm. “This is hypothesis-generating,” stated Dr Maraveyas.

No serious safety concerns related to dalteparin emerged during the trial. Yet

Many Questions Remain

Although this study provides convincing evidence for use of LMWH in advanced pancreatic cancer, there are lingering questions, such as the best drug to use and the optimal dose. Dr Maraveyas suggested discussing the risk of a clot with the patient, who may then be amenable to daily injections, which are somewhat uncomfortable.

ECCO/ESMO Abstract O-6503