Combination therapy of meloxicam, a selective COX-2 inhibitor, and interferon alfa in metastatic renal cell carcinoma: A phase II study on efficacy and toxicity

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5105-5105 ◽  
Author(s):  
N. Shinohara ◽  
T. Harabayashi ◽  
A. Sazawa ◽  
K. Nonomura ◽  
Y. Watarai ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Phase Ii ◽  
Renal Cell ◽  
Overall Response Rate ◽  
Response Rate ◽  
Antitumor Effects ◽  
Overall Response ◽  
Cox 2 ◽  
Metastatic Rcc

5105 Background: Cyclooxygenase (COX)-2 plays a major role in the development of cancer through numerous mechanisms. We have previously confirmed that COX-2 is expressed in a renal cell carcinoma (RCC) and it has an important role in tumorigenesis and angiogenesis (Int J Cancer 2004). Some preclinical studies suggest that a selective COX-2 inhibitor may augment the antitumor effects of immunotherapeutic agents. We conducted a phase II trial of the combination of meloxicam, a selective COX-2 inhibitor, and interferon (IFN)-alfa 2a in metastatic RCC in order to test the hypothesis that meloxicam enhances the response to the immunotherapy. Methods: Eligible patients had metastatic RCC, no prior systemic therapy, performance status 0–2, measurable disease. Patients received IFN 3–5 MIU 3x/week and meloxicam 10 mg/daily orally. This was a single-stage trial. Primary end points were RECIST response rates and toxicity. Results: Twenty-one patients were enrolled. Patients characteristics included: median age 63 years (49–75), male/female: 16/5, PS 0/1/2: 11/6/4, prior nephrectomy: 16 (76%). MSKCC prognostic categories were good: intermediate: poor (24%: 48%: 29%). A median follow-up was 8 months (range 3–29+) and 18 of 21 (86%) patients are still alive. Toxicities were mostly grade 1 or 2 (fever, fatigue, anorexia, depression), except 1 patient with grade 3 liver dysfunction. Among 20 patients evaluable for response, complete response (CR) was observed in 3 patients (15%) and partial response (PR) in 5 (25%), yielding an overall response rate of 40% (95% CI: 17–63). An additional 5 patients (25%) had stable disease. Five of 6 patients classified as poor risk by MSKCC prognostic classification obtained a CR or PR, as did 3 of 14 patients as good or intermediate risk (p=0.038). Median time to progression for 20 patients was 6 months (1–29+). Conclusions: The overall response rate of 40% for the combination of meloxicam and IFN-alfa in metastatic RCC is greater than that of IFN-alfa alone reported previously, suggesting that meloxicam can enhance the response to immunotherapy. Further investigation with this combination is warranted. No significant financial relationships to disclose.

Response to systemic therapy in non-clear cell renal cell carcinomas: A systematic review and meta-analysis.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 425-425 ◽  
Author(s):  
Francisco Emilio Vera-Badillo ◽  
Arnoud Templeton ◽  
Alberto Ocana ◽  
Paulo deGouveia ◽  
Priya Aneja ◽  
...  
Keyword(s):  
Systematic Review ◽  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Systemic Therapy ◽  
Renal Cell ◽  
Overall Response Rate ◽  
Response Rate ◽  
Clear Cell ◽  
Meta Analysis ◽  
Cell Renal Cell Carcinoma

425 Background: Clinical data supporting the efficacy of systemic therapy in non-clear cell renal cell carcinoma (non-ccRCC) are limited and based on retrospective analyses, expanded access programs and single arm phase II trials. Therefore the optimal treatment for this subgroup remains uncertain. Methods: A systematic review of electronic databases was conducted to identify publications evaluating the outcomes of patients with non-ccRCC (excluding those with sarcomatoid tumors) treated with different systemic approaches (immunotherapy, chemotherapy, targeted agents, small molecules). The primary endpoint was response rate and secondary endpoints were median progression free (PFS) and overall survival (OS). Where possible, data were pooled in a meta-analysis using the Mantel-Haenszel random-effect modeling. For studies comprising of unselected patients, outcomes of those with non-ccRCC were compared with clear cell renal cell carcinoma (ccRCC). Results: Forty-nine studies comprising 7,799 patients were included: 471 patients were enrolled on studies conducted exclusively in non-ccRCC and 7,328 patients on studies of unselected renal cell carcinoma. Among these, 903 (12%) had non-ccRCC and 6,425 (88%) had ccRCC. For non-ccRCC, overall response rate, median PFS and median OS were 9%, 7.9 and 13.4 months, respectively. By comparison, the overall response rate for ccRCC was 15% (Risk Ratio for response [RR] 0.67, 95% CI 0.52-0.86, p=0.002). This association was independent of type of treatment administered. Among the different novel agents (bevacizumab, lenalidomide, linefanib, sorafenib, sunitinib, pazopanib, everolimus and temsirolimus), sunitinib was significantly less efficacious in non-ccRCC than ccRCC (RR 0.56, 95% CI 0.42-0.72), but there was no significant difference in response rates for sorafenib (RR 0.64, 95% CI 0.31-1.35) or other agents (RR 1.10, 95% CI 0.50-2.44), However, confidence intervals were wide. Results of further analyses will be presented at the meeting. Conclusions: Patients with non-ccRCC have lower response rates than those with ccRCC, but the absolute difference between them is modest. Further study of targeted therapy in non-ccRCC is warranted.

Immunotherapy of advanced renal cell carcinoma

1996 ◽  
Vol 63 (4) ◽  
pp. 451-457
Author(s):  
F. De Braud ◽  
T. De Pas ◽  
M. Maffezzini
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Overall Response Rate ◽  
Response Rate ◽  
Cost Benefit ◽  
Cytotoxic Chemotherapy ◽  
Advanced Renal Cell Carcinoma ◽  
Therapeutic Approaches ◽  
The Cost

Although many different treatments have been evaluated in the last thirty years, advanced renal cell carcinoma still has a poor prognosis, characterised by a survival rate which is less than 5% at 3 years from diagnosis. Many different therapeutic approaches have been carried out in addition to cytotoxic chemotherapy, which shows obvious limits such as an overall response rate that does not go above 10-15%. One of the more promising treatments that has been studied the most is undoubtedly immunotherapy. We present a literature review aimed at summing up all the results obtained until now with immunotherapy of renal cell carcinoma, whether alone or in combination with cytotoxic chemotherapy. Unanswered questions of major concern are stressed, such as treatment choice, dosage, the most convenient schedules with particular regard to the cost-benefit issue.

Phase II trial of interferon-beta-serine in metastatic renal cell carcinoma.

1990 ◽  
Vol 8 (5) ◽  
pp. 881-885 ◽  
Author(s):  
P Kinney ◽  
P Triozzi ◽  
D Young ◽  
J Drago ◽  
B Behrens ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Phase Ii ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Interferon Beta ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Cumulative Toxicity ◽  
High Doses

Interferon-beta-serine (IFN-beta-ser) is a muteine, recombinant IFN that is tolerated at a dose fivefold to 10-fold higher than IFN-alfa and interacts with the same cell membrane receptor as IFN-alfa. We hypothesized that at high doses IFN-beta-ser might induce a higher response rate than IFN-alfa in metastatic renal cell carcinoma. We undertook a phase II trial of IFN-beta-ser in patients with metastatic renal cell carcinoma. Patients were treated three times each week by a 2-hour intravenous infusion. Doses were escalated weekly (.25 to 5.5 mg, 1 mg = 180,000,000 U) until the maximum-tolerated treatment dose (MTTD) was determined. The MTTD is defined as one dose level less than that which caused grade 3 toxicity and was subsequently administered three times weekly for at least 4 weeks. Twenty-nine patients were entered, and 25 were assessable for response and toxicity. The performance status was 0-1 in all patients and only one patient received previous chemotherapy. The MTTD dose was 2.5 mg (range, 0.5 to 5.5 mg per treatment), although in 10 patients, doses were later deescalated because of cumulative toxicity. Initial dose-limiting toxicity and cumulative toxicity were fatigue, malaise, and fever in most patients. Hepatic transaminitis, neutropenia, and elevation of serum creatinine were also observed but were not dose-limiting. There was one complete response (CR) and four partial responses (PRs). All responses but one occurred in pulmonary metastases. The median time to response was 26 days (range, 17 to 102 days). These data demonstrate that IFN-beta-ser given in high doses exhibits significant antitumor activity in renal cell carcinoma; however, the objective response rate is 20%. This is no higher than previous IFN studies; therefore, we reject the hypothesis than IFN-beta-ser at high doses may induce a greater response rate than IFN-alfa. However, we did observe more responses than were seen in a similar trial undertaken with lower dose IFN-beta serine in renal cell carcinoma.

A phase II study of the cancer vaccine TG4010 alone and in combination with cytokines in patients with metastatic renal cell carcinoma (RCC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 2581-2581 ◽  
Author(s):  
E. Banu ◽  
O. Rixe ◽  
C. Linassier ◽  
J. P. Machiels ◽  
M. Baudard ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
T Cell ◽  
Cell Carcinoma ◽  
Phase Ii ◽  
Cancer Vaccine ◽  
Renal Cell ◽  
Interleukin 2 ◽  
T Cell Response ◽  
Interferon Α2a ◽  
Metastatic Rcc

2581 Background: MUC1 is a glycoprotein often over-expressed and underglycosylated in renal cell carcinoma (RCC) making it an attractive antigenic target for tumor-specific immunotherapy. TG4010 is a cancer vaccine based on a modified vaccinia virus, strain MVA, expressing both MUC1 and Interleukin 2 (MVA-MUC1-IL2). The objective of this phase II, non-randomized study was to determine the efficacy of TG4010 alone and in combination with cytokines. Methods: Thirty seven patients (pts) with progressive metastatic RCC expressing MUC1 in at least 50% of the tumour cells were treated by subcutaneous injections of TG4010, 108 pfu/inj weekly, for 6 weeks then every three weeks until progression. At progression, TG4010 was continued in combination with Interferon α2a (INF) and Interleukin 2 (IL2). Results: Treatment efficacy and toxicities were previously presented at ASCO 2005 (abstr 4653). No objective responses have been observed, however, 7 pts (19%) remained stable for more than 6 months with TG4010 alone, 3 of them more than 22 months. After progression on TG4010 alone 22 pts received TG4010 in combination with cytokines. Six pts (27%) have been stabilized more than 6 months. The median TTP were 2.6 months (95% CI, 2.4–2.9 months) for TG4010 alone and 3.5 months (95% CI, 0.2–6.7 months) for the combined treatment. There were 24 deaths, with a median OS of 19 months (95% CI, 10–27.9) for the whole population. Seven pts were treated by sorafenib after immunotherapy failure. After censoring pts at the introduction of sorafenib, the median OS was 16 months (95% CI, 6–26), with 41% of pts alive at 2-years. The most frequent adverse effects related to TG4010 were minor to moderate injection site reactions, fatigue and flu-like symptoms. Twelve out of 24 pts evaluable for MUC1 ELISpot show evidence for MUC1-specific CD8+ T cell response while 14 out of 21 evaluable for MUC1 specific T cell proliferation were responsive. Conclusions: The cancer vaccine TG4010 alone and in combination with IL2 and INF induces some disease stabilizations in pts with progressive metastatic RCC and can improve survival in a population selected for MUC1 positivity, which is a factor of poor prognosis. [Table: see text]

Efficacy and thyroidal effects of sunitinib in Japanese patients with metastatic renal cell carcinoma: Hypothyroidism and thyroid atrophy as potential biomarkers for sunitinib?

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16097-e16097 ◽  
Author(s):  
N. Shinohara ◽  
M. Takahashi ◽  
T. Kamishima ◽  
H. Ikushima ◽  
A. Sazawa ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Thyroid Gland ◽  
Cell Carcinoma ◽  
Thyroid Function ◽  
Phase Ii ◽  
Renal Cell ◽  
Tumor Response ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Potential Biomarkers

e16097 Background: Although hypothyroidism is a well-known adverse effect of sunitinib in western patients (pts) with metastatic renal cell carcinoma (MRCC), the effects on thyroid gland of sunitinib in Japanese pts still remain unclear. We therefore evaluated thyroid dysfunction and thyroid atrophy in Japanese RCC pts who received sunitinib. Methods: Fourteen (8 males, 6 females) of 51 pts who were treated in a phase II trial of sunitinib in Japanese pts with MRCC were included in this retrospective study. All 14 pts were euthyroid at baseline. The measurement of serum thyroid function test (fT3, fT4, TSH) was performed at the beginning of each sunitinib treatment cycle. A TSH concentration greater than 10 mU/L was considered as hypothyroidism regardless of subclinical or clinical. CT volumetry of the thyroid gland was performed utilizing the data obtained for tumor assessment in a phase II trial. Tumor response was evaluated based on the RECIST criteria. Results: 9 (64%) of 14 pts achieved RECIST-defined objective response (1 CR, 8 PRs). With regard to thyroid function, hypothyroidism was experienced by 11 (79%) pts. Three of 11 pts had Sunitinib-induced thyrotoxicosis before experiencing hypothyroidism. The mean time to development of hypothyroidism was 55 days (range 13–668). Six pts received typical doses of L-thyroxine. The response rate was 73% (8/11) in pts with hypothyroidism and 33% (1/3) in pts without. With regard to the volume of thyroid gland in 13 pts, 8 pts had more than 50% reduction comparing the volume at the baseline. Median reduction rate in volume of 13 pts was 57% (range 0–95%). Hypothyroidism was experienced by all 8 pts with more than 50% reduction in volume and 2 of 5 (40%) without. Furthermore, the response rate was 88% (7/8) in former pts and 40% (2/5) in latter pts. Conclusions: In addition to high anti-tumor efficacy, hypothyroidism and thyroid atrophy were commonly observed in Japanese MRCC pts who received sunitinib. Although further study should be required, these abnormal findings in thyroid gland following treatment with sunitinib may be potential biomarkers for tumor response to sunitinib. [Table: see text]

Phase II Trial of Thalidomide for Patients With Advanced Renal Cell Carcinoma

2002 ◽  
Vol 20 (1) ◽  
pp. 302-306 ◽  
Author(s):  
Robert J. Motzer ◽  
William Berg ◽  
Michelle Ginsberg ◽  
Paul Russo ◽  
Jacqueline Vuky ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Stable Disease ◽  
Renal Cell ◽  
Maximum Dose ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Advanced Renal Cell Carcinoma ◽  
Antitumor Effects ◽  
Metastatic Rcc

PURPOSE: To assess efficacy and toxicity of thalidomide in patients with advanced renal cell carcinoma (RCC). PATIENTS AND METHODS: Twenty-six patients with RCC were treated with thalidomide at a starting dose of 200 mg daily. Thalidomide was increased by 200 mg every 2 weeks until a maximum dose of 800 mg or prohibitive toxicity was reached. Fifteen patients had prior nephrectomy, 11 patients had no prior systemic therapy, and 15 had received one prior systemic regimen. RESULTS: A maximum dose of 800 mg, 600 mg, 400 mg, and 200 mg was reached in five, 10, eight, and three patients, respectively. Grade 2 and 3 dyspnea occurred in four and three patients, respectively. Grade 2 and 3 neurologic toxicity was observed in five and two patients, respectively. Of the 25 assessable patients, the best response was stable disease in 16 (95% confidence interval [CI], 43% to 82%) patients. The 6-month progression-free survival rate was 32% (95% CI, 14% to 50%). Three patients achieved prolonged stable disease of 16, 16+, and 18+ months, including two patients who were refractory to previous cytokine therapy. Fifty-seven percent were alive at 1 year (95% CI, 37% to 76%). CONCLUSION: This trial does not support the routine use of thalidomide to induce partial response for metastatic RCC. Because disease stabilization occurs as a part of the natural history of metastatic RCC, the potential effect of thalidomide on progression-free and overall survival for patients with advanced RCC is being addressed in a randomized phase III trial. New immunomodulatory analogs of thalidomide that have shown potentially greater antitumor effects in preclinical models warrant study in metastatic RCC.

scholarly journals Pembrolizumab for Platinum- and Cetuximab-Refractory Head and Neck Cancer: Results From a Single-Arm, Phase II Study

2017 ◽  
Vol 35 (14) ◽  
pp. 1542-1549 ◽  
Author(s):  
Joshua Bauml ◽  
Tanguy Y. Seiwert ◽  
David G. Pfister ◽  
Francis Worden ◽  
Stephen V. Liu ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Phase Ii ◽  
Squamous Cell ◽  
Overall Response Rate ◽  
Response Rate ◽  
Neck Squamous Cell Carcinoma ◽  
Overall Response ◽  
Programmed Death

Purpose There are no approved treatments for recurrent/metastatic head and neck squamous cell carcinoma refractory to platinum and cetuximab. In the single-arm, phase II KEYNOTE-055 study, we evaluated pembrolizumab, an anti–programmed death 1 receptor antibody, in this platinum- and cetuximab-pretreated population with poor prognosis. Methods Eligibility stipulated disease progression within 6 months of platinum and cetuximab treatment. Patients received pembrolizumab 200 mg every 3 weeks. Imaging was performed every 6 to 9 weeks. Primary end points: overall response rate (Response Evaluation Criteria in Solid Tumors v1.1, central review) and safety. Efficacy was assessed in all dosed patients and in subgroups on the basis of programmed death ligand 1 (PD-L1) expression and human papillomavirus (HPV) status. Results Among 171 patients treated, 75% received two or more prior lines of therapy for metastatic disease, 82% were PD-L1 positive, and 22% were HPV positive. At the time of analysis, 109 patients (64%) experienced a treatment-related adverse event; 26 patients (15%) experienced a grade ≥ 3 event. Seven patients (4%) discontinued treatment, and one died of treatment-related adverse events. Overall response rate was 16% (95% CI, 11% to 23%), with a median duration of response of 8 months (range, 2+ to 12+ months); 75% of responses were ongoing at the time of analysis. Response rates were similar in all HPV and PD-L1 subgroups. Median progression-free survival was 2.1 months, and median overall survival was 8 months. Conclusion Pembrolizumab exhibited clinically meaningful antitumor activity and an acceptable safety profile in recurrent/metastatic head and neck squamous cell carcinoma previously treated with platinum and cetuximab.

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