Metastatic disease renal cell

A Phase I/II clinical trial was conducted in 10 patients with metastatic tumors (renal cell carcinoma, colon carcinoma, melanoma). Tumor material from each patient was isolated, and the cells were ex vivo double-transfected using MIDGE vectors encoding GM-GSF and IL-7. Thereafter, the cells were irradiated and dSLIM added. This autologous therapeutic agent was injected into the patients four times at intervals of 14 days. At the injection site, the APCs were in contact with TAAs and immunomodulating molecules, and this led to a tumor-specific immune response. In total, 50% of the patients responded clinically to the therapy, exhibiting complete or partial response, or stable disease (Fig. 7.14) [60]. 

H. Other considerations Proleukin has been designated an orphan drug for use in the treatment of metastatic renal cell carcinoma, metastatic melanoma, non-Hodgkin s lymphoma, and primary immunodeficiency disease associated with T-cell defects. 

High-dose IL-2 is approved for the treatment of metastatic renal cell carcinoma. The tumor is intrinsically immunogenic, and can elicit a host immune response that infrequently results in spontaneous remission of disease administration of IL-2 is believed to augment the normal immune response [53]. In a Phase II study that supported the approval of high-dose IL-2 for this indication, 15% of patients achieved objective responses (8% were partial responses and 7% complete responses). In this trial, patients received IL-2 at 600 000 or 720 000 U/kg per dose. The cumulative dose and the efficacy were similar between dose groups patients receiving the higher dose tolerated fewer cycles of therapy due to toxicity. 

IL-2 has been used in the treatment of sohd tumors such as metastatic melanoma, metastatic renal cell carcinoma, and colorectal carcinoma. Interleukin-2 infusions are associated with significant dose-dependent toxicity characterized by fevers, malaise, nausea, vomiting, diarrhea, hepatic dysfunction, pulmonary edema, somnolence, confusion, dysrhythmias, myocardial infarction, hematopoietic suppression, and renal insufficiency [10]. IL-2 has a short serum half-life of 6-10 min and a clearance of 30-60 min after bolus intravenously infusion [11]. Resultant toxicity is generally transient and reversible. It is possible that IL-2 induced renal failure only occurs in the setting of profound hypotension, prior volume depletion, concurrent administration of potentially nephrotoxic drugs, or the presence of underlying renal disease. 

Baseline laboratory tests should be obtained and include a complete blood cell (CBC) count, platelet count, prothrombin time, activated partial thromboplastin time, and liver and renal function tests. Abnormal liver function tests may suggest liver involvement with tumor. However, patients with metastatic disease to the liver may have normal liver function tests, and abnormal liver function tests are not always indicative of metastatic disease. 

An inverse relationship between ErbB-1 and ErbB-2 levels in renal cell carcinoma has been shown (Weidner et al., 1990). ErbB-2 overexpression was noted with increased frequency in certain renal cystic disorders as well as in neoplasms (Herrera, 1991). Combined high expression of ErbB-1 and ErbB-2 was correlated with metastatic disease (Stumm et al., 1996). 

Several anticancer drugs are indoles, the most famous of which are the Catharanthus roseus plant alkaloids vinblastine (124) and vincristine (125) (Scheme 18), both of which continue to be important drugs for the treatment of Hodgkin s disease, childhood leukemia, and other cancers [141-143], The rebeccamycin analogue NSC-655649 (126) is in phase n trials for the treatment of metastatic renal cell cancer... 

Fig. 9.11a-f. Renal cell carcinoma in the residual kidney with hemorrhage, medically inoperable, a, b Before and after embolization with PVA and coils, c, d Repeat bleeding 1-1.5 years later pre- and postembolization with PVA, Gelfoam, and coils. e,f Repeat bleeding 9 months later pre- and post-Ethanol embolization. The patient survived for 5 more years before he succumbed to diffuse metastatic disease... 

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