A phase I study of temsirolimus plus carboplatin plus paclitaxel for patients with recurrent or metastatic (R/M) head and neck squamous cell cancer (HNSCC).

PURPOSE: The mammalian target of rapamycin complex 1 (mTORC1) is aberrantly activated in many head and neck squamous cell carcinomas (HNSCCs). This phase I study combines the mTORC1 inhibitor temsirolimus with carboplatin and paclitaxel. METHODS: This was a single institution phase I study for patients with R/M HNSCC with a standard 3 + 3 design. Three doses of temsirolimus were planned: 15, 20, and 25 mg. Due to excessive toxicity with the original study regimen, the protocol was amended to carboplatin AUC 1.5, paclitaxel 80 mg/m(2), and temsirolimus (according to dose escalation plan), all on days 1 and 8 of a 21-day cycle. RESULTS: 18 patients (14 male, 4 female) enrolled, with median age 56 years (range 33-78). The most common toxicities were anemia, leukopenia, thrombocytopenia, and hyperglycemia. Among all patients treated, the confirmed objective partial response (cPR) rate was 22 %. DLT was not exceeded among 6 patients treated at dose level 3 of the revised protocol, and 4 of 6 subjects treated at this dose level had cPRs. CONCLUSION: The phase II recommended regimen is temsirolimus 25 mg, carboplatin AUC 1.5, and paclitaxel 80 mg/m(2), all on days 1 and 8 of a 21-day cycle. A phase II study of this regimen in R/M HNSCC is ongoing.

Hemorrhagic pseudoaneurysm in a patient receiving aflibercept for metastatic thyroid cancer.

BACKGROUND: Agents such as aflibercept, which target the angiogenic pathway, are of great interest as candidates for the management of metastatic differentiated thyroid cancer. Here, we report a patient who developed a hemorrhagic abdominal pseudoaneurysm shortly after being started on this drug. PATIENT FINDINGS: The patient was a 67-year-old woman being treated with single agent aflibercept (VEGF-Trap) for metastatic thyroid cancer. She had no history of intra-abdominal pathology or vascular disease but had been previously treated with sorafenib. Twelve days after receiving her second dose of aflibercept, she developed vague abdominal pain, which increased in severity and was accompanied by nausea and vomiting. Her symptoms progressed along with a decline in her hematocrit and signs of internal hemorrhaging. An angiogram identified an occluded celiac artery with increased collaterals and a bleeding pseudoaneurysm in the inferior pancreaticoduodenal artery. After the pseudoaneurysm was coiled, the patient stabilized. SUMMARY AND CONCLUSIONS: Anti-angiogenic agents, usually well tolerated, can disrupt the delicate balance of normal endothelium, leading to hemorrhagic and thrombotic complications. The hemorrhage of aberrant vasculature should be included in the differential diagnosis in patients presenting with vague complaints while being treated with anti-angiogenic agents.

Phase II study of saracatinib (AZD0530) for patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC).

BACKGROUND: Saracatinib (AZD0530) is an orally available Src kinase inhibitor. A phase II study was conducted to evaluate saracatinib in patients with recurrent or metastatic head and neck squamous cell cancer (HNSCC). PATIENTS AND METHODS: This was an open-label, single-arm, phase II study. Patients received 175 mg saracatinib daily either orally or by percutaneous gastrostomy tube. Radiologic imaging for response was planned at the end of each eight-week cycle. RESULTS: Nine patients were enrolled. All patients had received prior radiotherapy and six patients had received prior chemotherapy for recurrent or metastatic disease. The most common adverse event was fatigue. Eight patients had progression of disease by response evaluation criteria in solid tumors (RECIST) within the first eight-week cycle and one patient was removed from the study after 11 days due to clinical decline with stable disease according to the RECIST criteria. Median overall survival was six months. The study was closed early due to lack of efficacy according to the early stopping rule. CONCLUSION: Single-agent saracatinib does not merit further study in recurrent or metastatic HNSCC.