Objective To determine whether the favorable outcome associated with human papillomavirus (HPV) 16-positive cancer is related to a patient’s adaptive immunity. Setting Academic medical center. Methods Forty-seven of 66 previously untreated patients (6 of 20 patients with stage II and 41 of 46 with stage IV cancer) in a prospective clinical trial of chemoradiotherapy. Intervention All patients were treated with a single course of neoadjuvant chemotherapy followed by either surgery (for non-responders) or concurrent chemotherapy and conventional radiation. Main Outcome Measures Pretreatment levels (percentages and absolute counts) of CD3, CD4, CD8, NK, and B cells and overall WBC were measured by flow cytometry. Correlations of subsets with HPV-16 status, tumor subsite, stage, T class, N class, smoking status, performance status, gender, response to chemoradiotherapy, p53 mutation type, epidermal growth factor receptor expression, and disease specific and overall survival were determined. Results After median follow up of 6.6 years, improved survival was associated with elevated percentage of CD8 levels (P=.04), a low CD4:CD8 ratio (P=.01), low epidermal growth factor receptor expression (P=.002), and HPV status (P=.02). The percentage of CD8 cell levels were significantly higher (P=.04) in HPV-16-positive patients. A higher percentage of CD8 cells was associated with response to induction chemotherapy (P=.02) and complete tumor response after chemoradiation (P=.045) Conclusions These findings confirm previous correlations of outcome with circulating CD8 cell levels and support the conjecture that improved adaptive immunity may play a role in the favorable prognosis of patients with HPV-16-positive cancers.

Purpose-Insulin-like growth factor 1 receptor signaling through upregulation of the stimulatory ligand IGF-II has been implicated in the pathogenesis of adrenocortical carcinoma. As there is a paucity of effective therapies, this dose expansion cohort of a phase 1 study was undertaken to determine the safety, tolerability, pharmacokinetics, and effects on endocrine markers of figitumumab in patients with adrenocortical carcinoma. NIH Public Access Author ManuscriptCancer Chemother Pharmacol. Author manuscript; available in PMC 2011 March 1. NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptMethods-Figitumumab was administered on day 1 of each 21-day cycle at the maximal feasible dose (20 mg/kg) to a cohort of patients with metastatic, refractory adrenocortical carcinoma. Serum glucose, insulin, and growth hormone were measured pre-study, at cycle 4 and study end. Pharmacokinetic evaluation was performed during cycles 1 and 4.Results-Fourteen patients with adrenocortical carcinoma received 50 cycles of figitumumab at the 20 mg/kg. Treatment-related toxicities were generally mild and included hyperglycemia, nausea, fatigue, and anorexia. Single episodes of grade 4 hyperuricemia, proteinuria, and elevated gammaglutamyltransferase were observed. Pharmacokinetics of figitumumab was comparable to patients with solid tumors other than adrenocortical carcinoma. Treatment with figitumumab increased serum insulin and growth hormone levels. Eight of 14 patients (57%) had stable disease.Conclusions-The side effect profile and pharmacokinetics of figitumumab were similar in patients with adrenocortical carcinoma in comparison to patients with other solid tumors. While hyperglycemia was the most common adverse event, no clear patterns predicting severity were observed. The majority of patients receiving protocol therapy with single agent figitumumab experienced stability of disease, warranting further evaluation.

FDG-PET may be as efficacious as endoscopy with biopsy under general anesthesia for estimating tumor volume reduction with induction chemotherapy.

One cycle of neoadjuvant chemotherapy was effective in selecting patients for organ preservation. The regimen of definitive concurrent and adjuvant chemotherapy was associated with an unexpectedly high 2-year survival rate. Lymphocyte subsets were not significant predictors of responding patients or survival. Further study of other biological markers useful in selecting patients for organ preservation are needed.

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