Pilot study of local @entity221 , radiation therapy, @entity11256 , and @entity900 for advanced superficial XXXX .

@entity1 @entity8 @entity137 @entity390 @entity440 @entity5 @entity11256 @entity900 @entity391 @entity1897 @entity1011 @entity221
Five @entity1 (six @entity221 sites) with advanced superficial @entity5 were treated with combined @entity11256 , @entity900 , local @entity221 , and radiation therapy as part of a Phase I pilot study. Treatment was given once weekly and consisted of @entity11256 3 gm/m2 IV bolus, @entity900 50 mg/m2 IV bolus, @entity221 for 60 min with a target temperature of 43 degrees C, and radiation therapy 500 cGy/fraction (median total dose 3000 cGy) for a total of six weeks. Blood levels of @entity11256 were taken during treatment at week 1 and week 4. @entity11256 drug exposure was calculated using the trapezoidal rule and expressed as the area under the curve (AUC) of plasma concentration x time. Five of six treatment sites had received prior irradiation. Prior chemotherapy had been given in three @entity1 and @entity440 therapy given in the other two @entity1 . The median follow-up time is 34 months; 3/5 @entity1 have died of disease. The most significant @entity137 was grade I or II @entity390 and @entity391 associated with 19/32 treatments (59%) and a second degree burn in 2/6 fields. None of the five @entity1 experienced @entity1897 , skin ulceration, or needed surgical repair. In addition, there was mild @entity8 ; pharmacokinetic analysis showed a 28-75% increase in the week 1 to week 4 AUC in three @entity1 , all of whom had a decrease in @entity1011 clearance over the same time of 15-47%. This pilot study suggests this combined modality therapy can be delivered without major complications and that renal function, determined by @entity1011 clearance, affects clearance of @entity11256 and alters the AUC. Therefore, monitoring renal function is important in @entity1 receiving @entity11256 in addition to other nephrotoxic agents such as @entity900 . The impact of @entity11256 on the therapeutic index of @entity221 , radiation therapy and @entity900 may be worth of study, especially since a positive interaction between these modalities is found in laboratory models.
