Lacey McQuinn

Preoperative factors predicting survival after secondary cytoreduction for recurrent ovarian cancer

Objective: We evaluated preoperative data that may predict benefit from secondary cytoreductive surgery (CRS) to assist in selecting therapy for patients with platinum-sensitive recurrent epithelial ovarian cancer. Materials and Methods: Inclusion criteria included recurrent epithelial or primary peritoneal carcinoma with an initial disease-free interval more than 6 months after chemotherapy, evidence of disease on imaging studies and indication for surgery being to debulk residual disease. Preoperative CA125 values, computed tomographic findings, and time to progression were evaluated as predictors of survival in addition to postoperative information and perioperative morbidity. Results: Sixty-two patients met the inclusion criteria. In the 35.5% of patients debulked to no visible disease, median survival was significantly longer than in those with less than 1 cm of visible residual disease (5.95 vs 2.73 years, P = 0.004), but debulking to less than 1 cm visible disease was not better than those with less than 1 cm residual disease (2.02 years). Mean preoperative CA125 levels were significantly lower in the patients who could be debulked to no visible residual disease compared to less than 1 cm or more than 1 cm residual disease (69.1 vs 290.7 vs 1978.4, P = 0.001). Generation of a receiver operating characteristic curve determined that a CA125 cutoff of 250 U/mL best predicted successful cytoreduction to no visible disease. Conclusions: Only patients cytoreduced to no visible disease achieved a survival advantage, and the only preoperative factor that could predict surgical success regarding prolonging survival was a CA125 less than 250 U/mL. These data can guide physicians and patients in deciding whether or not to undergo secondary cytoreduction for first recurrence of ovarian cancer.

Incidence of mucositis in patients treated with temsirolimus-based regimens and correlation to treatment response.

Mucositis may limit the therapeutic window for mammalian target of rapamycin inhibitor-based combination therapy, necessitating treatment interruptions and/or dose reductions. Optimizing treatment or prophylactic interventions for mucositis will enable patients to continue effective treatment while maintaining good quality of life.

Barriers to Study Enrollment in Patients With Advanced Cancer Referred to a Phase I Clinical Trials Unit

UNLABELLED We conducted this retrospective study to identify reasons that patients referred to a phase I clinical trial failed to enroll or delayed enrollment onto the trial. MATERIALS AND METHODS Outcome analyses were conducted independently on data collected from electronic medical records of two sets of consecutive patients referred to a phase I clinical trial facility at MD Anderson Cancer Center. Data from the first set of 300 patients were used to determine relevant variables affecting enrollment; data from the second set of 957 patients were then analyzed for these variables. RESULTS Results from the two sets of patients were similar. Approximately 55% of patients were enrolled in a phase I trial. Patients referred from within MD Anderson were more likely to be enrolled than patients seen originally outside the institution (p = .006); black patients were more likely than white patients to enroll (69% vs. 43%; p = .04). The median interval from the initial visit to initiation of treatments was 19 days. Major reasons for failure to enroll included failure to return to the clinic (36%), opting for treatment in another clinic (17%), hospice referral (11%), early death (10%), and lack of financial clearance (5%). Treatment was delayed for three weeks or more in 250 patients; in 85 patients (34%), the delay was caused by financial and insurance issues. CONCLUSION Failure to return to the clinic, pursuit of other therapy, and rapid deterioration were the major reasons for failure to enroll; lengthy financial clearance was the most common reason for delayed enrollment onto a phase I trial.

Prevalence of Complementary Medicine Use in Patients With Cancer: A Turkish Comprehensive Cancer Center Experience

Purpose Complementary and alternative medicine (CAM) has been popular among patients with cancer for several decades. The objectives of this study were to evaluate the prevalence of CAM use and to identify the factors affecting CAM use in a large patient cohort seen at a comprehensive cancer center in Turkey. Patients and Methods An investigator-designed survey was completed by volunteer patients who visited the outpatient clinic in the medical oncology department. CAM use encompassed pharmacologic agents including vitamins, dietary supplements, and herbal products or nonpharmacologic methods like prayer, meditation, hypnosis, massage, or acupuncture. Results Of 1,499 patients who answered the survey, 1,433 (96%) used nonpharmacologic CAM and 60 (4%) used pharmacologic CAM (pCAM). The most frequent types of CAM used were prayer (n = 1,433) followed by herbal products (n = 42). pCAM use was not significantly associated with age (P = .63), sex (P = .15), diagnosis (P = .15), or income level (P = .09). However, it was significantly associated with the level of education (P = .0067) and employment status (P < .001). Patients with higher education levels used more pCAM products (P = .025). Among 60 pCAM users, six patients (10%) used pCAM for more than 2 years and 22 (36%) did not consult their physicians about their pCAM use. Only nine patients (15%) reported unpleasant adverse effects related to pCAM. Conclusion Although CAM use was high among our patients, prevalence of pCAM use was lower than expected. Patients with higher education levels tended to use more pCAM.

Abstract CT406: Aerosol interleukin-2 for the treatment of patients ≥ 12 years old with osteosarcoma lung disease: A phase I/II study

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA The purpose of this study is to test aerosol delivery of Interkeukin-2 (IL-2) in patients > 12 yrs. with lung metastases to establish feasibility and safety in the pediatric population and determine the maximum tolerated dose (MTD) for potential combination therapies in patients with Osteosarcoma (OS) lung metastases. Organ-specific delivery of agents by the aerosol route offers many advantages for the treatment of OS since it targets the organ where metastases are and provides significantly less toxic effects. OS survival has remained at 65-70% for the last 20 years. Our pre-clinical data using a human OS mouse model demonstrated therapeutic efficacy of aerosol IL-2 in OS lung metastases (p = 0.03) and increase apoptosis measured by TUNEL (p= 0.003). In addition, aerosol IL-2 increased local immune cell proliferation as demonstrated by an increase in CD4+ T cells and NK cells with no evidence of T regulatory cells. Most recently, IL-2 was shown to induce autophagy, an evolutionary, conserved, intracellular self-defense mechanism, in CD4+ T cells and NK cells and contributes to growth factor withdrawal cell death. Inhibition of autophagy augments immune cell function allowing a better anti-tumor effect. Immunohistochemistry staining of OS lung tumors from mice treated with aerosol IL-2 showed an increase in Beclin expression as evidence of autophagy induction. We initiated a Phase I/II clinical trial of aerosol IL-2 to include patients > 12 years with lung metastases. The primary objective is to determine feasibility and safety of aerosol IL-2. The secondary objective is to determine local effects of aerosol IL-2 by analyzing pre and post-treatment surgical samples for evidence of increase NK cell number, function and autophagy induction. Patients received aerosolized IL-2 for 3 consecutive weeks (21 day cycle) for 2 cycles with 1-week rest between cycles providing no drug limiting toxicities (DLTs) occur. The first treatment is delivered in the hospital. Subsequent treatments are given at home providing patients had been educated. From dose levels 1-4 only 1-patient/dose level was enrolled. From dose level 5 on, 3 patients will be enrolled. Once MTD is reached an additional 14 patients will be treated. 34 to 56 patients may be enrolled. Clinical response will be assessed by chest CT and determined using modified Response Evaluation Criteria in Solid Tumor (RECIST) after 2nd cycle. Results: 5 patients have been enrolled, ages 18, 35, 66, 20 and 15; all male, 3 with Ewings Sarcoma and 2 with Osteosarcoma. No side effects had been detected and serum levels of IL-2 were only detected in the fourth patient but were very low. Conclusion: Aerosol IL-2 seems so far feasibly and safe. Completion of the Phase I will provide information on the maximum tolerated dose (MTD) to use on the Phase II where only patients with OS lung metastases will be enrolled. Culmination of this trial will provide the basis for future combination therapy trials. Citation Format: Nancy Beatriz Gordon, Najat Daw Bitar, Peter Anderson, Sergei Guma, Hsuan-Chu Chien, Lacey M. McQuinn, Joshua P. Hein, Ralph Zinner, Eugenie S. Kleinerman, Aung Naing. Aerosol interleukin-2 for the treatment of patients ≥ 12 years old with osteosarcoma lung disease: A phase I/II study. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr CT406. doi:10.1158/1538-7445.AM2014-CT406

Abstract A82: Feasibility and safety of aerosol IL-2 in patients with lung metastases for future combination therapies for the treatment of osteosarcoma lung metastases

Organ-specific delivery of agents by the aerosol route offers many advantages since it targets the organ where metastases are and provides significantly less toxic effects. The purpose of this study is to evaluate safety of aerosol IL-2 in patients > 12 yrs. with lung metastases to establish the maximum tolerated dose (MTD) to use for combination therapies with infused natural killer cells and/or autophagy inhibitors in patients with Osteosarcoma (OS) lung metastases. Lung metastases constitute the main cause of death in patients with OS. Survival has remained the same in the past 15 years. Using a human OS mouse model we demonstrated therapeutic efficacy of aerosol IL-2 in OS lung metastases (p = 0.03) and there was significant increase in apoptosis measured by TUNEL (p= 0.003). In addition, aerosol IL-2 significantly increased proliferation of local infused NK cells in the lungs (p= 0.03 and p=0.007 at 24 and 72 hours respectively) with no proliferation demonstrated in other organs including bone marrow. Moreover, immunocompetent mice treated with aerosol IL-2 had significant increase in the number of local NK cells in the lung and there was no evidence of T regulatory cells, a group of cells known to abrogate immune response. Additionally, there is recent evidence to suggest that IL-2 induces autophagy, an evolutionary, conserved, intracellular self-defense mechanism, in CD4+ T cells and NK cells and contributes to growth factor withdrawal cell death. Inhibition of autophagy augments immune cell function allowing a better anti-tumor effect. We initiated a Phase I/II clinical trial of aerosol IL-2 to include patients > 12 years with lung metastases. The primary objective is to determine feasibility and safety of aerosol IL-2. The secondary objective is to determine local effects of aerosol IL-2 by analyzing pre and post-treatment surgical samples for evidence of increase NK cell number, function and autophagy induction. Patients received aerosolized IL-2 for 3 consecutive weeks (21 day cycle) for 2 cycles with 1-week rest between cycles providing no drug limiting toxicities (DLTs) occur. The first treatment is delivered in the hospital. Subsequent treatments are given at home providing patients had been educated. From dose levels 1-4 only 1 patient/dose level was enrolled. From dose level 5 on, 3 patients will be enrolled. Once MTD is reached an additional 14 patients will be treated. 34 to 56 patients may be enrolled. Clinical response will be assessed by chest CT and determined using modified Response Evaluation Criteria in Solid Tumor (RECIST) after 2nd cycle. We have reached dose level 4 and the only side effects were grade 1 fatigue (n= 1), grade 1 cough (n= 2), and grade 1 wheezing (n=1) Adverse events were not attributed to the IL-2 therapy since symptoms resolved without intervention. Serum levels of IL-2 were undetectable in the first three patients. The fourth patient has detectable but low serum levels of IL-2. All patients had progressive disease. In conclusion, feasibility and safety of aerosol IL-2 therapy will set the ground for future combination therapies with NK cells and/or autophagy inhibitors as potential therapeutic options for patients with recurrent and resistant OS lung disease. Citation Format: Nancy B. Gordon, Peter Anderson, Sergei Guma, Hsuan-Chu Chien, Lacey M. McQuinn, Joshua P. Hein, Ralph Zinner, Eugenie S. Kleinerman, Aung Naing. Feasibility and safety of aerosol IL-2 in patients with lung metastases for future combination therapies for the treatment of osteosarcoma lung metastases. [abstract]. In: Proceedings of the AACR Special Conference on Pediatric Cancer at the Crossroads: Translating Discovery into Improved Outcomes; Nov 3-6, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;74(20 Suppl):Abstract nr A82.

Abstract C64: Clinical evaluation of aerosol IL-2 in patients with lung metastases to test feasibility and safety for future combination therapy using infused natural killer cells.

The purpose of this study is to determine safety of aerosol IL-2 in patients ≥12 yrs. with lung metastases to establish the maximum tolerated dose (MTD) to use for combination therapy with infused natural killer (NK) cells in patients with osteosarcoma (OS) lung metastases. OS survival has remained at 65-70% for the last 20 years. One recent therapeutic approach has been to use adoptive cell-therapy to non-specifically augment immune function in vivo. However, therapeutic efficacy of immune cells depends upon proliferation and persistence in the tumor area. Organ-specific delivery of interleukin-2 (IL-2) offers that benefit. We initiated a Phase I/II clinical trial of aerosol IL-2 to include patients ≥12 years with lung metastases. The primary objective is to determine feasibility and safety of aerosol IL-2. Patients only received aerosolized IL-2 for 3 consecutive weeks (21 day cycle) for 2 cycles with 1-week rest between cycles providing no drug limiting toxicities (DLTs) occur. Each patient is educated on treatment administration the first time in the hospital. Further treatments are administered at home and remote spirometry and pulse oximetry are recorded before each treatment. Data is downloaded on a web portal and captured into the patient9s medical record. We anticipated the maximum tolerated dose (MTD) to be at dose level 5. From dose levels 1-4 only 1 patient/dose level was enrolled. From dose level 5 on, 3 patients will be enrolled and the 3 x 3 model will be followed. Once MTD is reached an additional 14 patients will be treated at the MTD. 34 to 56 patients may be enrolled. Clinical response will be assessed by chest CT and determined using modified Response Evaluation Criteria in Solid Tumor (RECIST) after 2nd cycle. So far, 4 patients have been enrolled, ages 18, 35, 66, and 20; all male, 3 with Ewing9s Sarcoma and 1 with osteosarcoma. Side effects were grade 1 fatigue (n= 1), grade 1 cough (n= 2), and grade 1 wheezing (n=1). None of these adverse events have been attributed to the IL-2 therapy since symptoms resolved without intervention while on therapy. Serum levels of IL-2 in the first three patients were undetectable and they had progressive disease. The fourth patient is on treatment. Supporting this clinical study is pre-clinical data from our lab. Immunocompetent mice treated with aerosol IL-2 had significant increase in the number of local NK cells in the lung when compared with aerosol phosphate buffer saline (PBS) group. Using a human OS mouse model we demonstrated therapeutic efficacy of aerosol IL-2 in OS lung metastases when compared with aerosol PBS group (p = 0.03) and there was significant increase in apoptosis measured by TUNEL (p= 0.003). In addition, aerosol IL-2 significantly increased proliferation of local infused NK cells in the lungs when compared with aerosol PBS group (p= 0.03 and p=0.007 at 24 and 72 hours respectively) with no proliferation demonstrated in other organs including bone marrow. In conclusion, clinical evaluation of aerosol IL-2 therapy will potentially benefit patients with OS who succumb almost always due to lung disease and allow future combination therapy with infused NK cells. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):C64. Citation Format: Nancy B. Gordon, Peter Anderson, Sergei R. Guma, Hsuan-Chu Chien, Lacey M. McQuinn, Joshua P. Hein, Ralph G. Zinner, Eugenie S. Kleinerman, Aung Naing. Clinical evaluation of aerosol IL-2 in patients with lung metastases to test feasibility and safety for future combination therapy using infused natural killer cells. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr C64.

Evaluation of aerosol IL-2 in sarcoma patients with lung metastases for future combination therapy with infused natural killer cells

To circumvent significant toxicities associated with high dose systemic IL-2 treatment, organ-specific delivery such as inhalational IL-2 has been studied. Our pre-clinical data demonstrated therapeutic efficacy of aerosol IL-2 in a human OS mouse model with no toxicity. The number of OS lung metastases in the aerosol IL-2 treated group was significantly less than the aerosol PBS control group (p = 0.03). IHC of OS lung nodules from mice treated with aerosol IL-2 showed a significant increase in apoptosis measured by TUNEL compared to the aerosol PBS group (p= 0.003). Aerosol IL-2 significantly increased proliferation of local NK cells in the lungs compared with aerosol PBS group (p= 0.03 and p=0.007 at 24 and 72 hours respectively). There was no proliferation of NK cells in other organs and no effect on T reg. Since sarcoma metastasizes to the lung, aerosol delivery is a reasonable approach. The study is to determine the safety of aerosol IL-2 in patients > 12 yrs. (with emphasis on those < 18years) with lung metastases to establish the maximum tolerated dose (MTD) to use for combination therapy with infused natural killer (NK) cells in patients with Osteosarcoma (OS) lung metastases. Patients with lung metastases only received aerosolized IL-2 for 3 consecutive weeks (21 day cycle) for 2 cycles with 1-week rest between cycles. Each patient is educated to administer the treatment for the first time in the hospital. For further home treatments, remote spirometries as well as pulse oximetry are recorded before each treatment. Data is downloaded on a web portal for investigators to access and captured into the patient’s medical record. Results: Four patients (age 18-66); all male; 3 with primary diagnosis of Ewing’s Sarcoma and 1 with Osteosarcoma. Side effects were grade 1 fatigue (n= 1), grade 1 cough (n= 2), and grade 1 wheezing (n=1.). None of these adverse events have been attributed to the IL-2 therapy since symptoms resolved without intervention while on therapy. Serum levels of IL-2 determined by ELISA immune assay in the first three patients were undetectable but low level in the pt from the highest dose thus far. In conclusion, clinical evaluation of aerosol IL-2 therapy to determine feasibility and safety will potentially benefit patients with OS who succumb almost always due to lung disease and allow future combination therapy with infused NK cells.