Patients who respond well to interventions for their childhood cancers may face other aggressive cancers in young adulthood. While 80-90% of children with Fanconi anemia respond to hematopoietic cell transplantation (HCT), they have a 500- to 700- fold higher incidence of squamous cell carcinoma (SCC) during the ages of 24-40. The radiation treatments and chemotherapies for SCC rarely prevent their demise.
The researchers have been searching for a treatment that will prevent the development of SCC in this young population. In a Phase I pharmacokinetic study they have identified a reactive oxygen species (ROS) scavenger (Quercetin) which they think will ameliorate SCC progression and decrease ongoing DNA damage. This scavenger is also an effective chemopreventive agent against SCC in mice. Because quercetin is a naturally occurring substance found in deeply pigmented foods, it is well tolerated with few or mild side effects.
This is a unique multidisciplinary study to assess a safe and easy natural way to prevent or slow the progression of an aggressive cancer in a young compromised population.
In this Phase II study of Quercetin chemoprevention for squamous cell carcinoma (SCC), the team at Memorial Sloan Kettering Cancer Center will determine the efficacy of Quercetin in preventing/delaying SCC using various surrogate marker of DNA damage and SCC susceptibility. Quercetin is a natural product, is inexpensive, readily available and without any major toxicity even with long-term use. Although antioxidants are known for a long time, only more recently their positive effects have been explored using evidence based systematic approach. The strong preclinical data suggest that Quercetin participates in a number of complex mechanisms at cellular level and alter the balance of ROS and antioxidants in patients’ blood and oral mucosa. This balance is significantly disturbed in patients with FA and those who develop cancer in general.
45 patients with FA (38 post-transplant and seven non-transplanted) will be treated with oral quercetin using the effective dose identified in the recent Phase I study, for a total of two years and followed closely. The team will study changes in DNA damage/genomic instability from quercetin treatment in buccal mucosa of 10 / 26 patients with FA as surrogate markers of efficacy. Bilateral buccal brushings will be evaluated for micronuclei (MN), at the start, at one month and at the end of one year of quercetin therapy. These data will be used to confirm ongoing adequate suppression of genomic instability and DNA damage. Additional proof-of-concept correlative studies will also be performed. The impact of quercetin on DNA damage/genomic instability and ROS reduction in blood and saliva will serve as surrogate markers for prevention of SCC. They will also assess impact of Quercetin on the reduction of aldehyde load, and on changes in the oral microbiome (number and type of bacteria in the mouth). [Adapted from Dr. Mehta’s full grant application]