Table 3.

Study Methods: Individual Extraction of Each Manuscript

Author(s)	Title	Year	Sample Size	Strengths & Weaknesses	Limitations
Atkins MB, Lotze MT, Dutcher JP, et al	High-Dose Recombinant Interleukin-2 Therapy for Patients with Metastatic Melanoma: Analysis of 270 Patients Treated Between 1985 and 1993	1999	N = 270	Strength = large sample size; Weakness = 8 different protocols in 22 different treatment centers decreasing internal reliability, also varying IV IL-2 doses received by pts	Retrospective study, inability to control for variables
Capuron L, Ravaud A, Neveu PJ, Miller AH, Maes M, Dantzer R	Association between decreased serum tryptophan concentrations and depressive symptoms in cancer patients undergoing cytokine therapy	2002	N = 16	Weakness = small sample size, different treatment protocols, international study (France)	Subcutaneous and IV IL-2 in sample
Fyfe G, Fisher RI, Rosenberg SA, et al	Result of Treatment of 255 Patients with Metastatic Renal Cell Carcinoma Who Received High-Dose Recombinant Interleukin-2 Therapy	1995	N = 255	Strength = large sample size; Weakness = different doses, 7 phase 2 trials and 21 treatment facilities	Retrospective, inconsistency in treatment dose, and facility
Gitlitz BJ, Hoffman DMJ, Moldawer N, et al	Treatment of Metastatic Renal Cell Carcinoma with High-Dose Bolus Interleukin-2 in a Non-Intensive Care Unit: An Analysis of 124 Consecutively Treated Patients	2001	N = 124	Strength = all patients received same dose, one facility, grade 3 + 4 toxicities stated	N/A
Mavroukakis SA, Muehlbauer PM, White RL, Jr., et al	Clinical Pathways for Managing Patients Receiving Interleukin 2	2001	N/A, Clinical pathway	Strength = holistic approaches to IL-2 management	Not a research study
Musselman D, Royster EB, Wang M, Long Q, Trimble LM, Mann TK, Graciaa DS, McNutt MD, Auyeung NS, Oliver L, Lawson DH, Miller AH	The impact of escitalopram on IL-2-induced neuroendocrine, immune, and behavioral changes in patients with malignant melanoma: preliminary findings	2013	N = 20	Strength = prospective, randomized control trial, one clinical site, strong internal reliability and validity; Weakness = small sample size	Sample size
Rosenberg SA, Yang JC, Topalian SL, et al	Treatment of 283 Consecutive Patients With Metastatic Melanoma or Renal Cell Carcinoma Using High-Dose Bolus Interleukin 2	1994	N = 283	Strength = prospective, large sample size, all treated with same IL-2 regimen in same location, using same measurement scales; strong internal reliability and validity	N/A
Sparber AG, Biller-Sparber K	Immunotherapy and neuropsychiatric toxicity. Nursing clinical management consideration.	1993	N/A, Clinical pathway	Strength = Clinical overview of neurotoxic symptoms	Not a research study
Tarhini AA, Kirkwood JM, Gooding WE, Cai C, Agarwala SS	Durable complete responses with high-dose bolus interleukin-2 in patients with metastatic melanoma who have experienced progression after biochemotherapy	2007	N = 26	Strength = prospective, phase II trial, carried out on one inpatient unit with same protocols; Weakness = small sample size	N/A

Abbreviations: IL-2, Interleukin-2; IV, Intravenous; N, Number; N/A, Not applicable; Pts, Patients.