A Study of Dalteparin Prophylaxis in High-Risk Ambulatory Cancer Patients

VTE is an increasingly frequent complication of cancer and anti-cancer therapies. It is
associated with increased mortality and other significant adverse consequences. Risk factors
for VTE in the cancer population have been identified, and multiple studies have also shown
that VTE can be prevented in high-risk populations with the use of thromboprophylaxis. This
study evaluated the safety and efficacy of prophylaxis in a high-risk subgroup of cancer
patients identified by a validated risk model developed by us previously called the "Khorana
Score." Correlative studies evaluated the value of tissue factor as a predictive biomarker
of VTE. The purpose of this study was to conduct a prospective, randomized clinical trial
comparing the safety and efficacy of prophylaxis with dalteparin to no treatment in reducing
VTE in high-risk ambulatory cancer patients initiating chemotherapy and to establish the
value of TF as a predictive marker for VTE in ambulatory cancer patients receiving
chemotherapy.

PHACS was a randomized multi-center clinical trial. Eligible patients were enrolled and
underwent baseline screening ultrasonography of the lower extremities to rule out
pre-existing DVT and a chest CT scan to rule out PE. If negative, patients were then
randomized to receive either dalteparin 5000 units subcutaneously daily or observation for a
study period of 12 weeks. The first day of dalteparin prophylaxis coincided with the first
day of initiation of a new systemic chemotherapy regimen. The patients were seen every 4
weeks (±1 week) at the time of regularly scheduled chemotherapy cycle visits for serial
ultrasonography of lower extremities during study period (i.e. at 4, 8 and 12 weeks.) A
chest CT scan was performed at 12 weeks. Compliance was measured by asking patients about
missed doses at these 4-weekly visits as well as by asking patients to fill an injection
diary.

Inclusion Criteria:

- A histologic diagnosis of malignancy;

- At planned initiation of a new systemic chemotherapy regimen (including patients
starting on first chemotherapy or patients previously treated but starting on a new
regimen);

- A risk score for VTE ≥3 [assign score of 2 for very high risk sites of cancer
(stomach, pancreas), score of 1 for high risk site (lung, lymphoma, gynecologic,
bladder, testicular) and score of 0 for all other sites], hemoglobin <10 g/dL or
planned use of erythropoiesis stimulating agents, platelet count ≥350,000/mm3, total
leukocyte count > 11,000/mm3 or body mass index ≥ 35 kg/m2]. Any counts meeting
criteria drawn within 2 weeks prior to enrollment are considered acceptable.

- Age 18 years or older

- Provide written, informed consent.

Exclusion Criteria:

- Active bleeding or at high risk of serious bleeding complication in the opinion of
the investigator

- Diagnosis of primary brain tumor multiple myeloma, leukemia, or myelodysplastic
syndrome

- Planned stem cell transplant

- Life expectancy < 6 months

- Known allergy to heparin or LMWH

- Patient or caregiver incapable of daily self-injection

- Acute or chronic renal insufficiency with creatinine clearance < 30 mL/min

- History of heparin-induced thrombocytopenia

- Allergy to contrast agents

- Pregnancy

- Need for anticoagulant therapy

- Platelet count < 75,000/mm3