Jan H. Einhorn

Prospective Randomized Trial of the Treatment of Patients With Metastatic Melanoma Using Chemotherapy With Cisplatin, Dacarbazine, and Tamoxifen Alone or in Combination With Interleukin-2 and Interferon Alfa-2b

PURPOSE The combination of chemotherapy with immunotherapeutic agents such as interleukin-2 and interferon alfa-2b has been reported to provide improved treatment results in patients with metastatic melanoma, compared with the use of chemotherapy alone. We have performed a prospective randomized trial in patients with metastatic melanoma, comparing treatment with chemotherapy to treatment with chemoimmunotherapy. PATIENTS AND METHODS One hundred two patients with metastatic melanoma were prospectively randomized to receive chemotherapy composed of tamoxifen, cisplatin, and dacarbazine or this same chemotherapy followed by interferon alfa-2b and interleukin-2. Objective responses, survival, and toxicity in the two groups were evaluated at a median potential follow-up of 42 months. RESULTS In 52 patients randomized to receive chemotherapy, there were 14 objective responses (27%), including four complete responses. In 50 patients randomized to receive chemoimmunotherapy, there were 22 objective responses (44%) (P2 = .071), including three complete responses. In both treatment groups, the duration of partial responses was often short, and there was a trend toward a survival advantage for patients receiving chemotherapy alone (P2 = .052; median survival of 15.8 months compared with 10.7 months). Treatment-related toxicities were greater in patients receiving chemoimmunotherapy. CONCLUSION With the treatment regimens used in this study, the addition of immunotherapy to combination chemotherapy increased toxicity but did not increase survival. The use of combination chemoimmunotherapy regimens is not recommended in the absence of well-designed, prospective, randomized protocols showing the benefit of this treatment strategy.

Renal dysfunction associated with the administration of high-dose interleukin-2 in 199 consecutive patients with metastatic melanoma or renal carcinoma.

PURPOSE To describe the incidence and management of renal dysfunction associated with the use of high-dose interleukin-2 (IL-2) (as is currently approved) in the treatment of cancer patients. PATIENTS AND METHODS One hundred ninety-nine consecutive patients with metastatic renal carcinoma or melanoma were treated with intravenous bolus infusions of IL-2 alone (720,000 IU/kg) every 8 hours. RESULTS Patients received 310 courses (589 cycles) of therapy and most experienced oliguria, hypotension, and weight gain; 13% of cycles were discontinued due to increased serum creatinine levels. Creatinine values (mean pretherapy, 1.2 mg/dL) increased during therapy and peaked (mean, 2.7 mg/dL) approximately 1 day after discontinuation of the second cycle of IL-2. Off therapy, toxicities reversed promptly and creatinine values returned to baseline. Higher peak creatinine values occurred in patients with renal carcinoma (v melanoma), older patients, males (v females), and those who had undergone prior nephrectomy. These same patient subsets received fewer doses of IL-2, but clinical responses were not associated with creatinine values or number of IL-2 doses administered. Urinalyses showed the appearance of protein, bilirubin, RBCs, WBCs, and granular casts during therapy, which cleared completely on follow-up evaluation. CONCLUSION High-dose IL-2 can be safely administered to cancer patients. The associated renal dysfunction is transient and without evidence of intrinsic long-term renal damage. Practical guidelines for patient management have been identified.

The hematologic toxicity of interleukin-2 in patients with metastatic melanoma and renal cell carcinoma

Background. High dose interleukin‐2 (IL‐2) has been found to produce durable antitumor responses in some patients, benefiting most greatly those patients with melanoma and renal cell carcinoma. In this paper, the hematologic toxicity and changes resulting from high dose IL‐2 alone administered by intravenous bolus are discussed.

Patient-reported outcomes for determining prognostic groups in veterans with stage IV solid tumors starting systemic therapy.

48 Background: A Recursive Partitioning Analysis (RPA) prognostic algorithm based on quality of life and symptoms predicted 4 groups with distinct median survivals in patients with metastatic solid tumors receiving chemotherapy (ASCO 2013, Abst 9567). We update our findings. METHODS The RPA algorithm is based upon Karnofsky performance status (KPS), Functional Assessment of Cancer Therapy (FACT) physical well-being (PWB) subscale, and Memorial Symptom Assessment Scale Short Form (MSAS-SF) physical symptom distress (PHYS) subscale. Starting in 2007, a convenience sample of Veterans who were prescribed systemic treatment for their cancer was enrolled in an IRB approved protocol, and completed quality of life (FACT- G) and symptom (MSAS SF) questionnaires at the first cycle of treatment. We analyzed records of patients with stage IV metastatic solid tumors enrolled through June 2013, and determined survival as of June 15, 2014. Analyses were performed with STATA 11.0. RESULTS There were 97 patients(pts). The median age was 64 yrs, range 27-88. Males comprised 95 (98%) pts. First line chemotherapy was given to 78 (80%) pts. The most common primary sites were lung cancer 33 (35%), prostate 17 (17%) and colon 11 (11%) pts. Median KPS was 90% range 40-100%, PWB median 23 (range 6-28), and MSAS SF median PHYS 0.76 (range 0-3.2). Overall median survival was 285 days (range 6-2,358) and 80 pts (82%) had died. There was 1 pt in group 1, 58 in group 2, 12 in group 3, and 23 in group 4. The patient in group 1 had uterine sarcoma. Median survival (days) by RPA group was 155 for group 1, 177 for group 2, 292 for group 3, and 674 for group 4 (p=.011). CONCLUSIONS These preliminary findings suggest that this algorithm is capable of dividing patients with metastatic solid tumor who are starting systemic therapy into prognostic groups. Further development is indicated.

Comparison of outcomes of patients with hepatocellular carcinoma (HCC) over 2 consecutive decades for a VA population.

e14536 Background: Hepatocellular carcinoma (HCC) incidence is increasing in the United States. We compared the outcome of HCC patients (pts) over two consecutive decades for a VA population. METHODS In an IRB-approved protocol, we reviewed the records of pts with diagnosis (dx) of HCC seen at a VA Medical Center from 1/1/1990 to 12/31/2009. Demographics, Vietnam era (V) status, stage, alpha-fetoprotein (AFP) level at dx, hepatitis B (HBV) and C (HCV), heavy alcohol use (E), tobacco use (T), BMI, diabetes (DM), ferritin (F) level, and treatment modalities were reviewed. Cox survival regression analysis and tests of proportions were performed. RESULTS All were men. There were 42 pts were from the first decade (d1) (1990 to 1999) and 72 pts from the 2nd decade (d1) (2000 to2009). The median (M) age at dx was 62.25 yo (35-87) for the whole population (W). Comparison of two decades is shown in the table. For the second decade, more variables were analyzed: M BMI of 70 pts was 25.3 (16.9-42.4). 34 pts (47.2%) were Caucasian, 33 pts (45.8%) African American, and 5 pts (7%) others. 25pts (34.7%) has DM, 57 (79%) E use, and 61 (84.7%) T use. Two pts (2.78%) received transplant, 4 (5.56%) resection, 16 (22%) local therapy (L), and 11 pts (15.3%) systemic therapy. In univariate survival analysis, age (p<0.004), stage (p<0.0001), AFP (p<0.0017), F (p<0.002), and V (p<0.0001) were significant predictors of survival. In multivariate survival analyses that included stage, AFP, F, and V for W, stage (p<0.019), AFP (p<0.0008), and F (p<0.035) were significant predictors. CONCLUSIONS The incidence of hepatocellular carcinoma increased at this medical center. Pts were diagnosed at an earlier stage and survival improved in 2nd decade. Stage, AFP, and ferritin levels were independent predictors of survival. [Table: see text].