Effects of Implementing a Brief Family Nursing Intervention With Hospitalized Oncology Patients and Their Families in Germany: A Quasi-Experimental Study.

Family nursing, based on the Calgary Family and Intervention Models, was implemented in a German oncological inpatient unit to promote effective family functioning in the context of cancer care. The objective of this study was to investigate the effects of implementing family nursing care on several psychological and physical outcomes of patients and their family members. A quasi-experimental study with 214 patients with a cancer diagnosis and 122 family members was conducted. Findings indicate that the superiority of family nursing, when compared to traditional care, could not be confirmed with respect to patients' outcomes (psychological burden, social support, satisfaction with care) and family members' outcomes (psychological burden, physical complaints, satisfaction with care). Various factors, such as country-specific structures and challenges in implementing family nursing care on an inpatient unit, may have contributed to these findings. Further replication attempts in similar settings in other countries are needed to shed light on the factors impairing or promoting the implementation of family nursing in practice settings.

FOLFOXIRI Plus Panitumumab As First-Line Treatment of RAS Wild-Type Metastatic Colorectal Cancer: The Randomized, Open-Label, Phase II VOLFI Study (AIO KRK0109).

PURPOSE: This trial investigated the addition of panitumumab to triplet chemotherapy with fluorouracil/folinic acid, oxaliplatin, and irinotecan (FOLFOXIRI) in a two-to-one randomized, controlled, open-label, phase II trial in patients with untreated RAS wild-type (WT) metastatic colorectal cancer. PATIENTS AND METHODS: The primary end point was objective response rate (ORR) according to RECIST (version 1.1). The experimental arm (modified FOLFOXIRI [mFOLFOXIRI] plus panitumumab) was considered active if the ORR was ≥ 75%. The experimental ORR was compared with an estimated ORR of 60% based on historical data, verified by a randomized control group (FOLFOXIRI). The power of the trial was 80%, with a potential type I error of 0.05. Secondary end points included secondary resection rate, toxicity, progression-free survival, and overall survival. RESULTS: A total of 63 patients were randomly assigned to the experimental arm and 33 patients to the control arm. The ORR of the mFOLFOXIRI plus panitumumab arm exceeded 75% and was higher when compared with that of FOLFOXIRI (87.3% v 60.6%; odds ratio, 4.469; 95% CI, 1.61 to 12.38; P = .004). The secondary resection rate was improved with the addition of panitumumab (33.3% v 12.1%; P = .02). Progression-free survival was similar in the study arms, whereas overall survival showed a trend in favor of the panitumumab-containing arm (hazard ratio for death, 0.67; 95% CI, 0.41 to 1.11; P = .12). CONCLUSION: The addition of panitumumab to mFOLFOXIRI in patients with RAS WT metastatic colorectal cancer improved the ORR and rate of secondary resection of metastases and represents a treatment option in selected and fit patients in need of highly active first-line therapy. Future studies should determine whether the addition of panitumumab to mFOLFOXIRI prolongs survival.

Neoadjuvant plus adjuvant or only adjuvant nab-paclitaxel plus gemcitabine for resectable pancreatic cancer - the NEONAX trial (AIO-PAK-0313), a prospective, randomized, controlled, phase II study of the AIO pancreatic cancer group.

BACKGROUND: Even clearly resectable pancreatic cancer still has an unfavorable prognosis. Neoadjuvant or perioperative therapies might improve the prognosis of these patients. Thus, evaluation of perioperative chemotherapy in resectable pancreatic cancer in a prospective, randomized trial is warranted. A substantial improvement in overall survival of patients with metastatic pancreatic cancer with FOLFIRINOX and nab-paclitaxel/gemcitabine vs standard gemcitabine has been demonstrated in phase III-trials. Indeed nab-paclitaxel/gemcitabine has a more favorable toxicity profile compared to the FOLFIRINOX protocol and appears applicable in a perioperative setting. METHODS: NEONAX is an interventional, prospective, randomized, controlled, open label, two sided phase II study with an unconnected analysis of the results in both experimental arms against a fixed survival probability (38% at 18 months with adjuvant gemcitabine), NCT02047513. NEONAX will enroll 166 patients with resectable pancreatic ductal adenocarcinoma (≤ cT3, N0 or N1, cM0) in two arms: Arm A (perioperative arm): 2 cycles nab-paclitaxel (125 mg/m2)/gemcitabine (1000 mg/m2, d1, 8 and 15 of an 28 day-cycle) followed by tumor surgery followed by 4 cycles nab-paclitaxel/gemcitabine, Arm B (adjuvant arm): tumor surgery followed by 6 cycles nab-paclitaxel/gemcitabine. The randomization (1:1) is eminent to avoid allocation bias between the groups. Randomization is stratified for tumor stage (ct1/2 vs. cT3) and lymph node status (cN0 vs. cN1). Primary objective is disease free survival (DFS) at 18 months after randomization. Key secondary objectives are 3-year overall survival (OS) rate and DFS rate, progression during neoadjuvant therapy, R0 and R1 resection rate, quality of life and correlation of DFS, OS and tumor regression with pharmacogenomic markers, tumor biomarkers and molecular analyses (ctDNA, transcriptome, miRNA-arrays). In addition, circulating tumor-DNA will be analyzed in patients with the best and the worst responses to the neoadjuvant treatment. The study was initiated in March 2015 in 26 centers for pancreatic surgery in Germany. DISCUSSION: The NEONAX trial is an innovative study on resectable pancreatic cancer and currently one of the largest trials in this field of research. It addresses the question of the role of intensified perioperative treatment with nab-paclitaxel plus gemcitabine in resectable pancreatic cancers to improve disease-free survival and offers a unique potential for translational research. TRIAL REGISTRATION: ClinicalTrials.gov : NCT02047513, 08/13/2014.

A Prognostic Gene Signature Expressed in Primary Cutaneous Melanoma: Synergism With Conventional Staging.

BACKGROUND: Current clinico-pathological American Joint Committee on Cancer (AJCC) staging of primary cutaneous melanoma is limited in its ability to determine clinical outcome, and complementary biomarkers are not available for routine prognostic assessment. We therefore adapted a gene signature, previously identified in fresh-frozen (FF) melanomas and adjacent stroma, to formalin-fixed paraffin-embedded (FFPE) melanomas. The aim was to develop a gene expression profiling (GEP) score to define patient survival probability at the time of first diagnosis. METHODS: Expression of 11 FF melanoma signature genes was quantified by reverse transcription polymerase chain reaction in an FFPE melanoma training cohort (n = 125), corresponding to the combined FF melanoma training and validation cohorts. The resulting GEP score was validated technically and clinically in an independent FFPE melanoma cohort (n = 211). All statistical tests were two-sided. RESULTS: We identified a prognostic eight-gene signature in the tumor area (tumor and adjacent tissue) of AJCC stage I-III melanomas. A signature-based GEP score correlated with melanoma-specific survival (MSS; Kaplan-Meier analysis: P < .0001) was independent of tumor stage (multivariable regression analysis: P = .0032) and stroma content (<5%-90%) and complemented conventional AJCC staging (receiver operating characteristic curve analysis: area under the curve = 0.91). In the clinical validation cohort, the GEP score remained statistically significant (P = .0131) in a multivariable analysis accounting for conventional staging. The GEP score was technically robust (reproducibility: 93%; n = 84) and clinically useful, as a binary as well as a continuous score, in predicting stage-specific patient MSS. CONCLUSIONS: The GEP score is a clinically significant prognostic tool, contributes additional information regarding the MSS of melanoma patients, and complements conventional staging.

Age has no significant impact on overall survival and on treatment tolerability in relapsed stage IV cutaneous malignant melanoma patients receiving Cisplatin, Gemcitabine, and Treosulfan.

OBJECTIVES: We compared the efficacy and tolerability of cisplatin, gemcitabine, and treosulfan (CGT) therapy in younger patients (age, <60 years) and in elderly patients (age, ≥60 years) with pretreated relapsed American Joint Committee on Cancer stage IV cutaneous malignant melanoma. PATIENTS AND METHODS: A total of 91 patients at the age of 18 to 80 years, in relapse after first-, second-, or third-line therapy received 40 mg/m intravenous (i.v.) cisplatin, 1000 mg/m i.v. gemcitabine, and 2500 mg/m i.v. treosulfan on days 1 and 8. CGT-therapy was repeated every 5 weeks until progression of disease occurred. RESULTS: Younger (n = 49) and elderly (n = 42) patients showed a significant difference in disease stabilization in 25% versus 7% (P ≤ 0.05), as opposed to 69% versus 91% patients exhibiting disease progression. In contrast, the overall median survival probability was not significantly different (P = 0.8153). Neither treatment-related toxicity nor toxicity-associated dose reduction showed substantial differences. CONCLUSIONS: Our results demonstrated that CGT therapy could be safely administered to a patient up to age 80 years.

Bleomycin, vinorelbine and trofosfamide in relapsed stage IV cutaneous malignant melanoma patients.

PURPOSE: To evaluate the efficacy of bleomycin, vinorelbine, and trofosfamide (BVT) in 28 patients with pretreated relapsed AJCC stage IV cutaneous malignant melanoma. METHODS: Patients in relapse after first- or second-line therapy received 8 mg/m(2) intravenous (i.v.) bleomycin, 25 mg/m(2) i.v. vinorelbine, on days 1 and 6, each, and oral (p.o.) trofosfamide 60 mg/m(2)/day, days 1-7. BVT therapy was repeated every 5 weeks until progression of disease occurred. A maximum of six BVT cycles (mean, 2.2 cycles) was administered per patient. RESULTS: Three patients (11%) reached a partial response; 5 (18%) patients showed stable disease, and 20 (71%) patients progressed upon BVT therapy. Median overall survival of all 28 patients was 6 months (6-month survival rate, 52%). Patients with partial remission or stable disease (n = 8) exhibited a median overall survival of 10 months (6-month survival rate, 75%), while patients with disease progression (n = 20) showed a median overall survival of 3 months (6-month survival rate, 43%). Most side effects were limited to WHO grade I/II mild anemia, leucocytopenia, fatigue, nausea/vomiting, pain, and anorexia. WHO grade III/IV side effects occurred in 7% (anorexia) and 4% (fatigue) of patients. CONCLUSION: Treatment with BVT was efficient in 29% of pretreated relapsed stage IV cutaneous melanoma patients, with overall good tolerability and safety.

Increased expression of the tumor suppressor PLZF is a continuous predictor of long-term survival in malignant melanoma patients.

Promyelocytic leukemia zinc finger (PLZF) is a transcriptional repressor and tumor suppressor inhibiting melanoma cell growth in vitro and in vivo in animal models. In this study, we analyzed the impact of in vivo primary tumor gene expression of PLZF on the long-term survival of malignant melanoma patients. PLZF expression was assessed by using DNA microarray and real-time polymerase chain reaction analysis of 41 primary malignant melanomas from patients with a defined histology and a close to 20-year clinical follow-up, of 29 melanoma metastases, and of 6 different melanoma cell lines. Kaplan-Meier survival analyses, log-rank statistics and Cox regression analysis were employed to identify the impact of PLZF expression on long-term survival. We detected PLZF expression in 92% of primary melanoma tumors in vivo but not in melanoma cell lines in vitro. By univariate analysis, we identified: (1) PLZF mRNA expression < or = 10,000 mRNA copies/mug total tumor RNA, (2) Breslow tumor thickness >4 mm, and (3) American Joint Committee on Cancer stages IIC, IIIB, IIIC, and IV as statistically significant pretreatment risk factors. We defined a continuous prognostic index (i.e., risk score) for primary melanoma patients based on the regression coefficient of PLZF mRNA expression. Applying a cutpoint to the prognostic index at - 1.65, patients were assigned to one of two risk groups: low-risk patients (n = 28) with a median overall survival of 79 months (5-year survival of 61%) and high-risk patients (n = 13) with a median overall survival of 32 months (5-year survival of 23%) (p < 0.05). This is the first time that PLZF mRNA expression has been linked to a prognostic model for primary malignant melanoma patients to derive prognostic groups for clinical purposes (e.g., improved melanoma immunotherapies).

Peripheral blood neutrophils as independent immunologic predictor of response and long-term survival upon immunotherapy in metastatic renal-cell carcinoma.

The aim of this study was to evaluate the prognostic impact of pretreatment neutrophils, previously rendered statistically independent, on the response and on long-term survival of metastatic renal carcinoma patients treated with outpatient subcutaneous (s.c.) interleukin-2 (IL-2) and s.c. interferon (IFN)-alpha. We assessed a total of 495 patients receiving s.c. IL-2/s.c. IFN-alpha-based therapy. While 417 patients with neutrophil counts <6500 cells/microL at baseline achieved 30% objective responses and a median survival of 22 months, 78 patients with pretreatment neutrophil counts >or= 6500 cells/microL had 18% objective responses and a median survival of 9 months (p=0.0000). In conclusion, pretreatment peripheral blood neutrophils <6500/microL constitute an immunologic predictor of tumor response and long-term survival in metastatic renal-cell carcinoma patients treated with s.c. IL-2 and s.c. IFN-alpha-based regimens.

Cisplatin, gemcitabine and treosulfan is effective in chemotherapy-pretreated relapsed stage IV uveal melanoma patients.

PURPOSE: The efficacy of cisplatin, gemcitabine, and treosulfan (CGT) was evaluated in patients with chemotherapy pretreated relapsed AJCC stage IV uveal malignant melanoma. METHODS: Patients received i.v./intrahepatic cisplatin, i.v. gemcitabine, and i.v. treosulfan (CGT) on day 1 and 8 as first-line (n = 1), second-line (n = 9), third-line (n = 1) or fourth-line (n = 1) therapy. Cisplatin, gemcitabine, and treosulfan (CGT)-therapy was repeated every 5 weeks until progression of disease occurred. A maximum of six CGT-cycles (mean, 2 cycles) was administered per patient. RESULTS: No objective response was observed, six patients (50%) had stable disease and six (50%) patients progressed upon first reevaluation. Overall survival of all the 12 patients was 6 months. Patients with stable disease reached a median overall survival of 12 months, while patients with disease progression upon first reevaluation had a median overall survival of 4 months, only. Grade III/IV related hematotological side effects were experienced in six (leukopenia) and four (thrombocytopenia) patients. CONCLUSIONS: Treatment with CGT may lead to disease stabilization and prolonged survival in a substantial proportion of progressive stage IV uveal melanoma patients, even following heavy chemotherapy treatment.

Fractional polynomials in a new metastatic renal carcinoma continuous prognostic index involving histology, laboratory, and clinical predictors.

BACKGROUND: We analyzed the effect of histology and various clinical and laboratory predictors in a new continuous prognostic index for metastatic renal-cell carcinoma based on fractional polynomials. PATIENTS AND METHODS: We evaluated 322 metastatic renal-cell carcinoma patients treated with subcutaneous recombinant cytokine-based home therapies in consecutive trials. We evaluated papillary histology, along with age, disease localizations, C-reactive protein, and neutrophil count in a new prognostic index, which was based on the multivariable fractional polynomial (MFP) algorithm. RESULTS: The MFP model allowed us to divide patients into three risk groups, using seven selected significant prognostic factors: histology, neutrophils, C-reactive protein, bone metastases, liver metastases, lymph node metastases, and age. Using the multivariable fractional polynomial model, median overall survival for high-, intermediate-, and low-risk patients was 10 months (n=80), 23 months (n=162), and 41 months (n=80) (scheme A; p

GM-CSF plus antigenic peptide vaccination in locally advanced melanoma patients.

Twenty-four (24) pretreated patients with relapsed high-risk resected The American Joint Committee on Cancer (AJCC) stage IIA-IV melanoma received adjuvant peptide vaccinations derived from the melanosomal antigens MelanA/MART1, MAGE-1, gp100, and tyrosinase, according to patient tumor-associated human leukocyte antigen (HLA) restricted antigen expression, in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF). Pretreatment was comprised of surgery (n=23 primary tumor; n=23 metastases), local radiotherapy (n=2), immunotherapy (n=23), chemotherapy (n=10), and chemoimmunotherapy (n=1), respectively. All patients received peptide vaccines in an adjuvant setting. Seven (7) patients were relapse free for 3+ up to 25+ months. Of the patients exhibiting progressive disease (n=17), 13 patients developed metastases during vaccination (9 local, 4 distant), and 4 patients developed metastases (2 local, 2 distant) after finishing vaccine therapy. Two (2)-year local and distant metastases-free survival, 2-year distant metastases-free survival, and 2-year overall survival were calculated as 8.6%, 68%, and 85%, respectively. Vaccine treatment was well tolerated, with no severe side-effects. Twenty (20) of 24 patients developed local delayed-type hypersensitivity (DTH) reactions to synthetic peptide vaccination. Transient fever (n=2) and pain in muscle/bone (n=2) occurred rarely. In conclusion, antigenic peptide vaccination, combined with GM-CSF, is safe and may yield clinical benefits in relapsed high-risk resected melanoma patients.

Long-term maintenance therapy in interferon-alpha2a/interleukin-2-pretreated advanced renal-cell carcinoma patients.

PURPOSE: In this paper, we report on the long-term therapeutic efficacy of maintenance treatment in 12 advanced renal carcinoma patients. PATIENTS AND METHODS: Following prior systemic treatment with 8-week cycles of subcutaneous interferon- alpha2a (s.c. IFN-alpha2a) and subcutaneous interleukin-2 (s.c. IL-2)-based immunotherapy (5-day standard Atzpodien regimen), patients received prolonged maintenance treatment consisting of intermittent s.c. IFN-alpha2a and s.c. IL-2, combined with long-term daily peroral 13-cis-retinoic acid (p.o. 13cRA). RESULTS: Patients received a mean of 10 months (range, 0-27 months) of maintenance treatment. Median progression-free survival was calculated at 6 months (range, 0-61 months), and median overall suvival was 22 months (range, 2-65 months) from the start of maintenance therapy. Of 12 patients, 5 were still alive (> or = 60 months) and 2 patients remained progression-free (61 months) at last follow-up. Maintenance treatment was well or moderately tolerated. CONCLUSIONS: Maintenance treatment with s.c. IL-2/s.c. INF-alpha2a/p.o. 13-cRA may support long-term efficacy of prior s.c. IL-2/s.c. INF-alpha2a-based therapy in advanced renal carcinoma patients.

Metastatic renal carcinoma long-term survivors treated with s.c. interferon-alpha and s.c. interleukin-2.

AIM: The aim of this retrospective analysis was to identify common features of long-term survivors among 218 advanced renal cell carcinoma patients sequentially entered on subcutaneous-recombinant-cytokine- based therapies between 1988 and 1993. PATIENTS AND METHODS: All patients were treated with subcutaneous (s.c.) interferon-alpha2a (IFN-alpha2a) and s.c. interleukin-2 (IL-2) alone (n = 98 pts) or in combination with intravenous (i.v.) 5-fluorouracil (5-FU) (Atzpodien regimen; n = 120 pts); those patients who survived more than 10 years were classified as long-term survivors. RESULTS: Thirteen patients (6.3%) were identified as long-term survivors with a median follow-up of 141 months (range, 122-174 months). According to a validated model of known clinical predictors, the long-term survivor group consisted of 6 low-risk, 5 intermediate-risk, and 2 high-risk patients, respectively. Within their clinical course, 9 longterm survivors achieved a complete response with a median duration of 141 months (range, 91-161 months), 1 patient yielded a partial remission, and 3 patients achieved stable disease. Maximum response was observed between 2 and 40 months after treatment initiation (median, 4 months), while treatment time to maximum response ranged from 2 to 14 months (median, 4 months). There was no correlation between treatment time and maximum response. Overall, long-term survivors underwent treatment for 4 and up to 80 months (median, 8 months). CONCLUSION: Our data suggest that long-term survival of metastatic renal carcinoma patients beyond 10 years is independent of known clinical risk factors and treatment time. However, long-term survival of cytokine-treated, advanced renal cell carcinoma (RCC) patients remains a rare event and, thus, emphasizes the need for further investigations toward more effective therapies.

Dose-dependent treatment benefit in high-risk melanoma patients receiving adjuvant high-dose interferon alfa-2b.

UNLABELLED: This retrospective analysis of 150 consecutive high-risk melanoma patients treated with high-dose interferon alfa-2b at a single institution demonstrates similar relapse-free and overall survival data, as previously published from Eastern Cooperative Oncology Group (ECOG) and Intergroup trials. The data suggest at least a transient dose dependency of the treatment effect on relapse-free and overall survival with high-dose interferon in high-risk melanoma patients. BACKGROUND: Adjuvant high-dose interferon seems to be the best adjuvant treatment option for patients with high-risk melanoma (AJCC-stage IIC, III) after definitive surgery. METHODS: One-hundred fifty consecutive patients were treated at our institution during the period from September 1997 to March 2003 were retrospectively studied. RESULTS: After a median follow-up of 35 months, 63% of patients had developed a melanoma relapse, and 37% were relapse- free. Fifty-five percent of patients are still alive, and 45% had died-all but 3 patients from melanoma. Patients with stage IIC disease demonstrated a similar unfavorable course of disease as patients with stage IIIC disease (2-year relapse-free survival 18% and 26%). We identified two groups of patients with different cumulative interferon dose-levels (> or =90% and <90% of the projected dose, according to the protocol), who demonstrated at least transient differences, both in terms of relapse-free and overall survival; the predictive impact was statistically independent upon the Cox regression analysis. CONCLUSIONS: Our clinical data are consistent with the published ECOG and Intergroup data dealing with highdose interferon in high-risk melanoma patients. The data suggest a dose-dependency on the treatment effect and, therefore, support further prospective trials comparing different dose-distribution patterns in high-dose interferon.

Predictive impact of retinoid X receptor-alpha-expression in renal-cell carcinoma.

PURPOSE: Retinoid receptors are nuclear transcription factors that mediate the effects of retinoids on gene expression. In our study, we analyzed the expression of retinoid X receptor-alpha (RXR-alpha) and its prognostic value in renal-cell carcinoma (RCC) patients exhibiting stage IV disease upon first diagnosis or thereafter. MATERIALS AND METHODS: Detection of RXR-alpha was performed on tumor specimens from 63 patients with primary RCC, using immunohistochemical techniques. For our evaluation of the immunostaining results, we developed a new cell-counting system based on the subcellular distribution of immunoreactivity. The impact of the subcellular distribution of RXR-alpha on the prognosis of patients with RCC was analyzed statistically among other clinicopathologic factors. The primary end point was survival. RESULTS: In 34 RCC samples (54.0%), RXR-alpha was detected predominantly in the nucleus, while 25 RCC specimens (39.7%) displayed an aberrant subcellular distribution pattern, with a predominantly cytoplasmic staining with nuclear sparing in 15 specimens (23.8%), and a combined nuclear and cytoplasmic staining in 10 specimens (15.9%). Very faint to undetectable immunoreactivity was noted in 4 cases (6.3%) of RCC. Univariate Kaplan-Meier analysis showed that patients with a predominantly nuclear localization of RXR-alpha had a significantly prolonged survival after primary tumor diagnosis, when compared to patients with a predominantly aberrant subcellular distribution profile (p < 0.01). Furthermore, multivariate analysis revealed that an aberrant subcellular distribution of RXR-alpha in RCC was an independent predictor of poor survival (p < 0.01). CONCLUSIONS: Our study indicated that the subcellular intratumoral distribution pattern of RXR-alpha could independently predict the survival of RCC patients. However, the exact mechanisms underlying the aberrant compartmentalization and the functions of RXR-alpha in RCC remain to be determined.

Individualized synthetic peptide vaccines with GM-CSF in locally advanced melanoma patients.

We report on 10 patients with resected American Joint Committee on Cancer (AJCC)stage IIA-IIIC melanoma receiving individualized adjuvant peptide vaccinations derived from the melanosomal antigens MelanA/MART1, gp100 and tyrosinase, according to patient tumor associated HLA restricted antigen expression, in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF). Except for 1 patient, all patients had received systemic pretreatment with immunotherapy (n = 8), chemoimmunotherapy (n = 1), chemotherapy (n = 1), or cefalectin therapy (n = 1). Upon prior therapy, 7 of 10 patients had progressed with subcutaneous/cutaneous (n = 2), lymph node (n = 3), or subcutaneous/cutaneous and lymph node (n = 2)metastases, which were subsequently resected prior to vaccination. After a mean of 6.5 vaccination cycles, progression-free survival was 6 months (median, range 2-10). Five patients were relapse-free for 1+ up to 21+ months, 3 patients developed a solitary cutaneous metastasis, and 2 patients developed multiple metastases during vaccination. Overall, vaccine treatment was well tolerated, with no severe side-effects. Eight of 10 patients developed local delayed type hypersensitivity (DTH)reactions to synthetic peptides after the first or second injection. In 2 patients, transient fever, nausea, diarrhea, and muscle pain of National Cancer Institute (NCI)Grade I occurred. In summary, individualized synthetic peptide vaccination, combined with GM-CSF, was feasible and warrants further clinical investigation.

Thirteen-year, long-term efficacy of interferon 2alpha and interleukin 2-based home therapy in patients with advanced renal cell carcinoma.

BACKGROUND: The goal of the current report was to demonstrate the long-term efficacy of outpatient subcutaneous (sc) interferon alpha (IFN-alpha) and sc interleukin 2 (IL-2)-based combination regimens in patients with metastatic renal cell carcinoma. METHODS: In three consecutive clinical trials, 443 patients received combined sc IFN-alpha and sc IL-2 (n = 97 patients); combined sc IFN-alpha, sc IL-2, and intravenous (iv) 5-fluorouracil (5-FU) (n = 260 patients); or combined sc IFN-alpha, sc IL-2, and iv 5-FU with oral 13cis-retinoic acid (n = 86 patients). RESULTS: The median overall survival was 21+ months. The 2-year, 5-year, and 13-year survival rates were calculated at 45.26%, 15.96%, and 8.96%, respectively. The median time to disease progression was 6 months. The 2-year, 5-year, and 13-year progression free survival rates were 17.84%, 9.54%, and 9.20%, respectively. CONCLUSIONS: The current data suggest that combined outpatient sc IFN-alpha and sc IL-2, according to the Atzpodien regimen, achieves long-term survival benefits in a subset of patients with metastatic renal cell carcinoma, both with and without 13-cis-retinoic acid and/or 5-fluorouracil.