Abstract
The primary objective of this study was to quantify the impact of treatment delay and dose reductions in an in vivo orthotopic ovarian cancer model. In addition, this study evaluated the role of growth factors in achieving “full dose on time”. HeyA-8 and SKOV3.ip1ovarian cancer orthotopic mouse models were used determine the effect of paclitaxel/carboplatin treatment delays or dose reductions on tumor response and overall survival. The addition of growth factor support with pegfilgrastim and darbepoetin was also evaluated in treatment control arm. The results indicated that full dose of paclitaxel (20 mg/kg) and carboplatin (50 mg/kg) delivered on time (every 21 days) achieved better tumor response in both aggressive (HeyA-8) and metastatic (SKOV3.ip1) human ovarian tumors compared to treatment delay or dose reduction arms. In the HeyA-8 orthotopic model treatment delay (P<0.05) resulted in a significant reduction in overall survival compared to on time, full dose treatment control arm and the dose reduction decreased overall survival but was not statistically significant. However, in the SKOV3.ip1orthotopic model a treatment delay (P<0.01) or dose reduction (P<0.05) both resulted in a significant reduction in overall survival compared to on time, full dose treatment control arm. In both orthotopic models, the addition of pegfilgrastim (1000 µg/kg) and darbepoetin (10 µg/kg) delayed the onset of ascites formation and was associated with an improved overall survival rate. Treatment delays and dose reductions had a negative impact on tumor response and overall survival compare with on-time, full dose treatment controls. In addition, use of growth factor agents improved overall survival and tumor responses.
Highlights
Ovarian cancer is the most lethal gynecological cancer and the fifth most common cause of malignancy in women [1]
Anemia is another common development during chemotherapy that is responsible for dose reductions and treatment delays; and prevention of anemia has been suggested to improve treatment outcomes both efficacy and quality of life
A summary of the impact of dose reductions and treatment delays on the overall survival rate of the HeyA-8 and SKOV3.ip1 tumor bearing mice is reported in Figure 2 and Table 1
Summary
Ovarian cancer is the most lethal gynecological cancer and the fifth most common cause of malignancy in women [1]. The current standard of care includes primary tumor debulking surgery followed by cytotoxic chemotherapy with 70% of patients achieving a complete initial clinical response. In addition to increasing the risk of developing febrile neutropenia, prolonged neutropenia often leads to delays in treatment and dose reductions of planned chemotherapy [7,8]. Anemia is another common development during chemotherapy that is responsible for dose reductions and treatment delays; and prevention of anemia has been suggested to improve treatment outcomes both efficacy and quality of life. New and improved growth factor support with agents such as pegfilgrastim and darbepoetin alfa have the potential to improve the management of chemotherapy-induced neutropenia and anemia, respectively [13]
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