Lung Homotransplantation in ManTHE TECHNICAL FEASIBILITY of lung replantation and homotransplantation in animals was established by the work of previous investigators.<sup>1, 2</sup>It was found that occasionally a dog could survive temporarily on the function of the lung homotransplant alone, especially if the respiratory reflexes from the unexcised lung had been preserved. Preservation of these reflexes with exclusion of pulmonary function in this "normal" or contralateral lung was achieved by ligation of the pulmonary artery on this side. In addition to studies demonstrating that either a reimplanted lung or a homotransplanted lung could function fairly effectively to provide a significant degree of pulmonary function, the use of various agents in dogs to suppress the immune response had permitted substantial prolongation of the survival of lung homografts. In our own experience, the lung homograft had been rejected in untreated dogs in an average of from seven to eight days, whereas in dogs
A phase II trial of intra-patient dose-escalated sorafenib in patients (pts) with metastatic renal cell cancer (MRCC)R. J. Amato, Patricia Harris, Martin L. Dalton et al.|Journal of Clinical Oncology|2007 5026 Background: Sorafenib has demonstrated activity with limited toxicity at a dose of 400 mg bid in MRCC pts. This presents an opportunity to explore a more intensive drug administration. This study allowed individual pt titration designed to evaluate the ability for pts to dose escalate. Response rate (RR), time to progression (TTP) and overall survival (OS) will be assessed. Methods: Eligibility included; pathologic diagnosis of a component of clear cell, progressive measurable MRCC, no more than 1 prior therapy, karnofsky performance status (KPS) = 70%, adequate organ/marrow function and no active CNS involvement. Initial dose 400 mg bid, daily. Dose escalation defined in the table below: Re-evaluation is performed every 8 weeks. RECIST criteria is utilized. Results: 46 patients have been enrolled. 44 are evaluable. 37 male/7 female, median age 50 years (43–79). 19 pts received prior therapy. 39 pts had a KPS of 100%, 5/90%. Sites of disease included; lung, nodal, liver, bone, adrenal, pancreas and kidney. 26 pts 1 metastatic site, 12 /2, 6/3 or more. 22 pts continue to receive sorafenib therapy; 2/800 mg, 7/1,200 mg, and 13/1,600 mg. 8 pts complete response (CR), 14 pts/partial response (PR) and 14 pts stable for 3+ months. Median duration of therapy is 6+ (range 0.2+ - 12+) months. 2 pts have not been reevaluated. Treatment related adverse events to-date; hand/foot syndrome, skin rash, diarrhea, alopecia, fatigue, hypertension, hypophosphatemia, and elevated amylase/lipase. Conclusion: 91% of pts were escalated to 1,200 mg or 1,600 mg per day. Dose escalated sorafenib has promising anti-tumor activity in pts with MRCC as demonstrated by a 52% CR/PR rate. Anti-tumor activity is further suggested by prolonged TTP = 3 months for 33% of pts. Independent radiology review is in progress. Intra-patient dose escalation data in association with anti-tumor activity and toxicity will be presented. [Table: see text] [Table: see text]