Final results of a phase II study of erlotinib, docetaxel and cisplatin in patients with recurrent/metastatic head and neck cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 6013-6013 ◽  
Author(s):  
E. S. Kim ◽  
M. S. Kies ◽  
B. S. Glisson ◽  
A. Tsao ◽  
L. E. Ginsberg ◽  
...  
Keyword(s):  
Growth Factor ◽  
Head And Neck ◽  
Response Rate ◽  
Kinase Inhibitor ◽  
Performance Status ◽  
Treatment Options ◽  
Single Agent ◽  
Progression Free Survival ◽  
Egfr Signaling Pathway ◽  
Grade 3

6013 Background: Interrupting the epidermal growth factor receptor (EGFR) signaling pathway has shown promise in a variety of cancers and preclinical data has demonstrated possible synergy with platinums and taxanes. Treatment options for recurrent/metastatic HNSCC are limited. A study of cisplatin and docetaxel showed a response rate of 40% and 9.6 month median survival. Erlotinib, an EGFR tyrosine kinase inhibitor, had a 4.3% response rate as single agent in HNSCC. Because of the possible synergy and efficacy, we proposed to study the combination of cisplatin, docetaxel and erlotinib in advanced HNSCC. Methods: Patients (pts) were required to have adequate performance status, measurable disease, no prior EGFR therapy, and may have received prior induction, concomitant or adjuvant chemotherapy, but not for recurrent/metastatic disease. Sites of disease included squamous cell head and neck sites excluding nasopharynx and sinus. Treatment included docetaxel 75 mg/m2 and cisplatin 75 mg/m2 intravenously every 3 weeks and erlotinib 150 mg by mouth daily. All agents were started on day 1. Pts were treated with growth factor support. Results: The trial has completed accrual to 50 pts. 47 pts are available for analysis at this time. Median age is 56 years (range 39–72). ECOG PS is 0, 1, 2 (6, 29, 2 pts). 43 pts are evaluable for efficacy. All responses were confirmed via RECIST. Complete responses have been in observed in 4 pts, partial responses in 25 pts and 12 pts have stable disease for an overall response rate of 67% and disease control rate of 95%. After a follow-up of 19 months, median overall survival was 11 months (8.61, 22.5, 95% CI) and progression free survival was 6.01 months (4.37, 8.25). 6 pts had grade 3/4 febrile neutropenia, 4 pts had grade 3/4 dehydration, 3 pts had grade 3 diarrhea, and 2 pts had grade 3/4 GI bleeding. The most common grade 1–2 toxicities were diarrhea, nausea, and rash. Conclusions: The combination of cisplatin, docetaxel and erlotinib is well tolerated and has very encouraging activity in recurrent/metastatic HNSCC. Tissues are being collected and analyzed for correlative markers including downstream EGFR pathway markers (p-akt, mek, k-ras). Final efficacy and biomarker results will be presented at the annual meeting. No significant financial relationships to disclose.

Phase II study of combination cisplatin, docetaxel and erlotinib in patients with metastatic/recurrent head and neck squamous cell carcinoma (HNSCC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 5521-5521 ◽  
Author(s):  
E. S. Kim ◽  
M. S. Kies ◽  
B. S. Glisson ◽  
L. E. Ginsberg ◽  
F. C. Holsinger ◽  
...  
Keyword(s):  
Growth Factor ◽  
Head And Neck ◽  
Squamous Cell ◽  
Response Rate ◽  
Kinase Inhibitor ◽  
Performance Status ◽  
Full Data ◽  
Data Set ◽  
Egfr Signaling Pathway ◽  
Grade 3

5521 Background: Interrupting the epidermal growth factor receptor (EGFR) signaling pathway has shown promise in a variety of cancers and preclinical data has demonstrated possible synergy with platinums and taxanes. Treatment options for advanced or recurrent HNSCC are limited. A study of cisplatin and docetaxel showed a response rate of 40% and 9.6 month median survival. Erlotinib, an EGFR tyrosine kinase inhibitor, had a 4.3% response rate in HNSCC. Because of the possible synergy and efficacy, we proposed to study the combination of cisplatin, docetaxel and erlotinib in advanced HNSCC. Methods: Patients (pts) were required to have adequate performance status, measurable disease, no prior EGFR therapy, and may have received one regimen of induction, concomitant or adjuvant chemotherapy, but not for recurrent/metastatic disease. Sites of disease included squamous cell head and neck sites excluding nasopharynx and sinus. Treatment included docetaxel 75mg/m2 and cisplatin 75mg/m2, intravenously every 3 weeks and erlotinib 150 mg by mouth daily. Patients were treated with growth factor support. Results: 37 pts have been enrolled thus far. Median age is 56 years (range 39–72). Median ECOG PS is 1 (range 0–2). 32 pts are evaluable for confirmed response using RECIST criteria. Complete responses have been in observed in 3 pts, partial responses in 18 pts and 8 pts have stable disease for an overall response rate of 66% and disease control rate of 91%. Only 2 pts progressed after 2 cycles of treatment. 5 pts had grade 3/4 neutropenia (2 febrile),1 pt had grade 4 diarrhea, and 2 pts had grade 3 rash. The most common grade 1–2 toxicities were diarrhea, nausea, and rash. Conclusion: The combination of cisplatin, docetaxel and erlotinib is well tolerated and has very encouraging activity in advanced HNSCC. Data collection for response rate, duration of response and survival is ongoing. Trial accrual continues up to 50 patients and biopsies are being collected for correlative markers including downstream EGFR pathway markers (p-akt, mek, k-ras). The full data set will be presented at the annual meeting. [Table: see text]

scholarly journals Phase III Randomized, Placebo-Controlled Trial of Docetaxel With or Without Gefitinib in Recurrent or Metastatic Head and Neck Cancer: An Eastern Cooperative Oncology Group Trial

2013 ◽  
Vol 31 (11) ◽  
pp. 1405-1414 ◽  
Author(s):  
Athanassios Argiris ◽  
Musie Ghebremichael ◽  
Jill Gilbert ◽  
Ju-Whei Lee ◽  
Kamakshi Sachidanandam ◽  
...  
Keyword(s):  
Head And Neck ◽  
Disease Progression ◽  
Kinase Inhibitor ◽  
Performance Status ◽  
Single Agent ◽  
Eastern Cooperative Oncology Group ◽  
Phase Iii ◽  
Oncology Group ◽  
Ecog Performance Status ◽  
Grade 3

Purpose We hypothesized that the addition of gefitinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, to docetaxel would enhance therapeutic efficacy in squamous cell carcinoma of the head and neck (SCCHN). Patients and Methods Patients with recurrent or metastatic SCCHN with Eastern Cooperative Oncology Group (ECOG) performance status of 2, or patients with ECOG performance status of 0 to 2 but were previously treated with chemotherapy, were randomly assigned to receive weekly docetaxel plus either placebo (arm A) or gefitinib 250 mg/d, orally (arm B) until disease progression. At the time of progression, patients in the placebo arm could receive single-agent gefitinib. EGFR, c-MET, and KRAS mutations and polymorphisms in drug metabolizing enzymes and transporters were evaluated by pyrosequencing. Results Two hundred seventy patients were enrolled before the study was closed early at interim analysis (arm A, n = 136; arm B, n = 134). Median overall survival was 6.0 months in arm A versus 7.3 months in arm B (hazard ratio, 0.93; 95% CI, 0.72 to 1.21; P = .60). An unplanned subset analysis showed that gefitinib improved survival in patients younger than 65 years (median 7.6 v 5.2 months; P = .04). Also, there was a trend for improved survival in patients with c-MET wild-type (5.7 v 3.6 months; P = .09) regardless of treatment. Grade 3/4 toxicities were comparable between the two arms except that grade 3/4 diarrhea was more common with docetaxel/gefitinib. Of 18 eligible patients who received gefitinib after disease progression in arm A, one patient had a partial response. Conclusion The addition of gefitinib to docetaxel was well tolerated but did not improve outcomes in poor prognosis but otherwise unselected patients with SCCHN.

scholarly journals Osimertinib Rechallenge With Bevacizumab vs. Chemotherapy Plus Bevacizumab in EGFR-Mutant NSCLC Patients With Osimertinib Resistance

2022 ◽  
Vol 12 ◽  
Author(s):  
Qingli Cui ◽  
Yanhui Hu ◽  
Qingan Cui ◽  
Daoyuan Wu ◽  
Yuefeng Mao ◽  
...  
Keyword(s):  
Growth Factor ◽  
Kinase Inhibitor ◽  
Treatment Options ◽  
Acquired Resistance ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Vegf Inhibitors ◽  
Clinical Benefits ◽  
Grade 3 ◽  
Egfr Mutant

At present, treatment options for osimertinib resistance are very limited. Dual inhibition of the vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) significantly improved the progression-free survival (PFS) of advanced EGFR-mutant non–small cell lung cancer (NSCLC). After EGFR-tyrosine kinase inhibitor (TKI) resistance, EGFR-TKI continuation combined with VEGF inhibitors still had clinical benefits. It is unclear whether the addition of bevacizumab after osimertinib progresses will prolong the duration of the osimertinib benefit. We screened 1289 patients with NSCLC and finally included 96 patients to evaluate osimertinib combined with bevacizumab (osi + bev) versus chemotherapy combined with bevacizumab (che + bev) for patients with acquired resistance to osimertinib. The overall response rate (ORR) for osi + bev and chem + bev was 15.8% (6 of 38) and 20.7% (12 of 58), respectively. The median PFS for osi + bev and che + bev was 7.0 and 4.9 months (HR 0.415 95%CI: 0.252–0.687 p = 0.001). The median OS for osi + bev and che + bev was 12.6 and 7.1 months (HR 0.430 95%CI: 0.266–0.696 p = 0.001). Multivariate analyses showed that no brain metastases and osi + bev treatment after osimertinib resistance correlated with longer PFS (p = 0.044, p = 0.001), while the median PFS of osimertinib less than 6 months (p = 0.021) had a detrimental effect on sequent treatment. Only osi + bev treatment was identified as an independent predictor of OS (p = 0.001). The most common adverse events (AEs) of grade ≥3 were hypertension (13.2%) and diarrhea (10.5%) in the osi + bevacizumab group. Neutropenia (24.1%) and thrombocytopenia (19%) were the most common grade ≥3 AEs in the che + bev group. The overall incidence of serious AEs (grade ≥3) was significantly higher in the chemotherapy plus bevacizumab group. Our study has shown the superiority of osi + bev compared to che + bev after the failure of osimertinib, making it a preferred option for patients with acquired resistance to osimertinib.

Chemotherapy Options for Patients With Metastatic or Recurrent Squamous Cell Carcinoma of the Head and Neck

2006 ◽  
Vol 24 (17) ◽  
pp. 2644-2652 ◽  
Author(s):  
A. Dimitrios Colevas
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Performance Status ◽  
Treatment Options ◽  
Single Agent ◽  
Clinical Trial Data ◽  
Progression Free Survival ◽  
Recurrent Squamous Cell Carcinoma

The purpose of this review is to provide readers with guidance concerning treatment of patients with advanced, recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) in the context of clinical trial data. We discuss issues surrounding the treatment of patients with SCCHN, with an emphasis on recommendations based on results from phase II and III clinical trials published since 1980. Many options exist for the treatment of patients with SCCHN. The most important decisions involve determining which patients are in need of treatment and which are most likely to benefit from treatment. Although many chemotherapy treatments have been shown to induce responses, survival improvement remains an unfulfilled goal. Definitive data do not exist on the effects of chemotherapy on quality of life or progression-free survival as measures of clinical benefit in this setting. Performance status, history of prior treatment, extent of tumor, and need for palliation are the most important factors in the decision to treat a patient with chemotherapy for incurable SCCHN. Single-agent treatment with conventional doses of methotrexate remains a standard for most patients with advanced, recurrent or metastatic SCCHN. Cisplatin plus fluorouracil, cisplatin plus a taxane, and single-agent taxane are the most widely studied alternatives. There is a need for further trials with end points other than overall survival or tumor response in this patient population. Guidelines for patient selection and treatment options are provided.

Sorafenib plus interferon-α2b (IFN) as first-line therapy for advanced renal cell carcinoma (RCC): SWOG 0412

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4525-4525 ◽  
Author(s):  
C. W. Ryan ◽  
B. H. Goldman ◽  
P. N. Lara ◽  
T. M. Beer ◽  
H. A. Drabkin ◽  
...  
Keyword(s):  
Overall Response Rate ◽  
Response Rate ◽  
Kinase Inhibitor ◽  
Performance Status ◽  
Progression Free Survival ◽  
Response Assessment ◽  
Common Side Effect ◽  
Overall Response ◽  
Hand Foot Syndrome ◽  
Grade 3

4525 Background: Sorafenib is a RAF and multiple receptor tyrosine kinase inhibitor active in RCC. IFN has modest activity in RCC and has immunologic, anti-angiogenic, and anti-proliferative effects. Sorafenib and IFN may simultaneously target anti-angiogenic and MAP kinase pathways, providing the basis for this phase II combination study. Methods: Eligible patients (pts) had metastatic or unresectable RCC with a clear cell component, no prior systemic therapy, performance status 0–1, measurable disease. Treatment: IFN 10 x 106 IU s.c. 3x/week and sorafenib 400 mg p.o. BID. Response assessment was performed q8 weeks. This was a single-stage trial with a planned sample size of 55. Primary endpoint was RECIST response rate. Results: Of 67 registered pts, 58 are eligible & evaluable. Pt characteristics: median age 61 years (42–84), male:female (40:18), prior nephrectomy 86%. MSKCC prognostic categories (42 pts) were good:intermediate:poor (28%:67%:5%). With a median follow-up of 6.5 months, 79% (46/58) of pts are alive, 41% (24/58) remain on treatment. Assessment of progression-free survival is premature. Overall response rate (53 pts) is 19% (95% CI: 9%, 32%) with CR 2% and PR 17% (9% confirmed, 8% unconfirmed). Toxicities affecting >50% of subjects were: fatigue, anorexia, diarrhea, nausea, rigors/chills, fever, anemia, leukopenia. Most common Grade 3+ toxicities were fatigue (24%), leukopenia (10%), anorexia (6%), diarrhea (6%), hyponatremia (6%). All pts experienced some toxicity, with 36 (62%) experiencing at least one Grade 3+ toxicity. Hand-foot syndrome, a common side effect of sorafenib, was seen in only 10% of pts. Conclusions: The overall response rate of 19% for the combination of sorafenib and IFN in advanced RCC is greater than expected with either IFN or sorafenib alone. Toxicity is typical of IFN and notable for minimal hand-foot syndrome. Further studies with this combination are warranted. [Table: see text]

Phase II study of gefitinib in patients with metastatic/recurrent squamous cell carcinoma of the skin

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 5531-5531 ◽  
Author(s):  
B. S. Glisson ◽  
E. S. Kim ◽  
M. S. Kies ◽  
M. Francisco ◽  
G. R. Blumenschein ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Response Rate ◽  
Kinase Inhibitor ◽  
Radiation Treatment ◽  
Performance Status ◽  
Cell Cancer ◽  
Egfr Signaling Pathway ◽  
Grade 3

5531 Background: Interrupting the epidermal growth factor receptor (EGFR) signaling pathway has shown promise in a variety of cancers. Skin squamous cell cancer (SCC) has been increasing in incidence at the rate of 4% to 8% per year since the 1960s, with especially increased rates (up to 10% annually) in recent years. Treatment options for advanced or recurrent skin SCC are extremely limited. Patients (pts) who fail surgery, radiation and/or chemotherapy have a very poor prognosis. Because of the importance of EGFR in tumorigenesis, and its overexpression in squamous cell carcinoma of the skin, it is an interesting target for treatment intervention. Gefitinib, an EGFR tyrosine kinase inhibitor, had a 11% response rate in HNSCC. Because of the possible efficacy, we proposed to study gefitinib in advanced skin SCC. Methods: Pts were required to have pathologically confirmed skin SCC adequate performance status, measurable disease, no prior EGFR therapy, and may have received prior chemotherapy. Pts must not have been amenable for curative intenet therapy with surgery or radiation. Treatment included gefitinib 250mg orally daily for 4 weeks. Results: 18 pts have been enrolled and 17 are evaluable. Median age is 68 years (range 37–84). Median ECOG PS is 1 (range 1–2). 12 pts are men and 5 women. 15 pts are currently evaluable for response. No objective partial responses were observed per WHO criteria. 4 pts (27%) have stable disease. Clinical responses were noted in 2 pts via photographs and clinical inspection. 17 pts are evaluable for toxicity. 2 pts had grade 3 rash and 1 pt had grade 3 keratitis. The most common grade 1–2 toxicities were diarrhea and fatigue. Conclusions: Gefitinib is well tolerated and has modest activity in advanced skin SCC. These pts have very few options for therapy. Data collection for response rate, duration of response and survival is ongoing as several patients are still receiving treatment. [Table: see text]

Randomized Phase II Trial of First-Line Trastuzumab Plus Docetaxel and Capecitabine Compared With Trastuzumab Plus Docetaxel inHER2-Positive Metastatic Breast Cancer

2010 ◽  
Vol 28 (6) ◽  
pp. 976-983 ◽  
Author(s):  
Andrew M. Wardley ◽  
Xavier Pivot ◽  
Flavia Morales-Vasquez ◽  
Luis M. Zetina ◽  
Maria de Fátima Dias Gaui ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Response Rate ◽  
Performance Status ◽  
Locally Advanced ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
First Line ◽  
Her2 Positive ◽  
Grade 3

PurposeTo evaluate trastuzumab (H) and docetaxel (T) with or without capecitabine (X) as first-line combination therapy for human epidermal growth factor receptor 2 (HER2) -positive advanced breast cancer.Patients and MethodsPatients with HER2-positive locally advanced or metastatic breast cancer were randomly assigned to H (8 mg/kg loading; 6 mg/kg every 3 weeks) plus T (75 mg/m2in HTX arm, 100 mg/m2in HT arm, every 3 weeks) with or without X (950 mg/m2twice per day on days 1 to 14 every 3 weeks). The primary end point was overall response rate (ORR).ResultsIn 222 patients, median follow-up was approximately 24 months. ORR was high with both regimens (70.5% with HTX; 72.7% with HT; P = .717); complete response rate was 23.2% with HTX compared with 16.4% with HT. HTX demonstrated significantly longer progression-free survival: median 17.9 months compared with 12.8 months with HT (hazard ratio, 0.72; P = .045), which translates to a gain of around 5 months. Two-year survival probability was 75% with HTX compared with 66% with HT. Febrile neutropenia (27% v 15%) and grade 3/4 neutropenia (77% v 54%) incidences were higher with HT than HTX. Treatment-related grade 3 hand-foot syndrome (17% v < 1%) and grade 3/4 diarrhea (11% v 4%) occurred more commonly with HTX than HT. One case of congestive heart failure occurred in each arm.ConclusionHTX is an effective and feasible first-line therapy for HER2-positive locally advanced or metastatic breast cancer, although it should be reserved for patients with good performance status who are not receiving long-term steroids.

A comparison of carboplatin plus methotrexate versus methotrexate alone in patients with recurrent and metastatic head and neck cancer.

1989 ◽  
Vol 7 (9) ◽  
pp. 1341-1345 ◽  
Author(s):  
M Eisenberger ◽  
S Krasnow ◽  
S Ellenberg ◽  
H Silva ◽  
J Abrams ◽  
...  
Keyword(s):  
Head And Neck ◽  
Ethical Issues ◽  
Response Rate ◽  
Performance Status ◽  
Single Agent ◽  
Active Agent ◽  
Dose Schedule ◽  
Substantial Improvement ◽  
Two Stage ◽  
Study Objective

Patients with recurrent and metastatic squamous cell carcinoma of the head and neck (SCCHN) were stratified by performance status, extent of disease, and prior radiotherapy and subsequently randomized to receive carboplatin (CBDCA; Bristol-Myers, Wallingford, CT) administered intravenously (IV) monthly, initially at doses of 400 mg/m2 in combination with methotrexate (MTX) given IV weekly at doses of 40 mg/m2 or MTX alone at the same dose/schedule. Significant dose-limiting myelosuppression required CBDCA dose reductions to 300 mg/m2 and, subsequently, 200 mg/m2. Nonhematological toxicities were not significant. Our study objective was to determine whether CBDCA plus MTX produce a substantial improvement in response rate over single-agent MTX. A response rate of 50% (complete [CR] plus partial response [PR]) for CBDCA plus MTX compared with 25% for MTX was specified as the difference to be detected. We employed a two-stage study design for randomized trials that allowed for early termination of studies involving relatively ineffective treatment regimens. With this design, the study could be closed after the first stage (20 patients entered onto each treatment arm) if the number of responders to CBDCA plus MTX were not superior to MTX. Five of 20 patients responded to treatment in each arm, and we were able to conclude that the addition of CBDCA to MTX is unlikely to result in a twofold increase in response rate compared with MTX alone in this group of patients. This two-stage design represents a simple and efficient method of testing the relative efficacy of new combinations containing at least one active agent against a suitable control arm in this disease. It addresses scientific and ethical issues of continuing testing with relatively ineffective treatments, and at the same time provides a reliable method for identifying very active regimens likely to represent significant therapeutic advances.

scholarly journals Toxicity management of regorafenib in patients with gastro-intestinal stromal tumour (GIST) in a tertiary cancer centre

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Florence Chamberlain ◽  
Sheima Farag ◽  
Constance Williams-Sharkey ◽  
Cecilia Collingwood ◽  
Lucia Chen ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Progression Free Survival ◽  
Individual Risk ◽  
Duration Of Treatment ◽  
Ecog Performance Status ◽  
Third Line ◽  
Grade 3 ◽  
Dose Reductions

Abstract Background Regorafenib is a multi-kinase inhibitor approved as third line treatment for metastatic GIST. Dose limiting toxicities are frequently seen and many patients require dose reductions. This study aimed to evaluate regorafenib toxicities and their management in a real-world GIST population. Methods Retrospective review of a prospectively maintained database identified 50 patients with GIST treated with regorafenib at our centre between March 2013 and September 2018. Results Median progression free survival (PFS) was 7.7 months [interquartile range (IQR) 2.8–14.4 months]. Median overall survival (OS) from start of regorafenib to death or last follow up was 15.7 months (IQR 9.2–28.4 months). Baseline median Eastern Cooperative Oncology Group (ECOG) performance status on starting regorafenib was 1. The main reason for discontinuing regorafenib was progressive disease (PD) (31/50 [62%]) rather than toxicity (10/50 [20%]). Grade 3–4 adverse events (AEs) were seen in 23/50 (46%) patients; palmar-plantar erythrodysesthesia (PPE) was most frequently seen (9/50 (18%)). Two patients died whilst on treatment with regorafenib from multi-organ failure secondary to sepsis (4%). Dose reductions were required in 19/50 patients (38%) and 8/50 (16%) patients started regorafenib at a lower dose band than the recommended dose (160 mg) due to comorbidities or concern over a higher individual risk of toxicity. Conclusion Although PD was the main reason for discontinuing treatment, toxicity management and dosing of regorafenib remains critical. Median duration of treatment was longer compared to previous studies suggesting a durable clinical benefit with regorafenib with rigorous toxicity management.

Sorafenib With Interferon Alfa-2b As First-Line Treatment of Advanced Renal Carcinoma: A Phase II Study of the Southwest Oncology Group

2007 ◽  
Vol 25 (22) ◽  
pp. 3296-3301 ◽  
Author(s):  
Christopher W. Ryan ◽  
Bryan H. Goldman ◽  
Primo N. Lara ◽  
Philip C. Mack ◽  
Tomasz M. Beer ◽  
...  
Keyword(s):  
Adverse Events ◽  
Phase Ii ◽  
Renal Carcinoma ◽  
Response Rate ◽  
Kinase Inhibitor ◽  
Phase Ii Study ◽  
Performance Status ◽  
Combined Treatment ◽  
Progression Free Survival ◽  
Interferon Alfa

Purpose This phase II study evaluated the activity of combined treatment with interferon alfa-2b and sorafenib, a Raf and multiple receptor tyrosine kinase inhibitor, in patients with advanced renal carcinoma. Patients and Methods Eligible patients had metastatic or unresectable renal carcinoma with a clear-cell component, no prior systemic therapy, performance status 0 to 1, and measurable disease. Treatment consisted of interferon alfa-2b 10 × 106 U subcutaneously three times weekly and sorafenib 400 mg orally bid. The primary end point was confirmed Response Evaluation Criteria in Solid Tumors response rate. Results Twelve (19%) of 62 assessable patients achieved an objective confirmed response. An additional 31 (50%) had an unconfirmed partial response or stable disease as best response. The median progression-free survival was 7 months (95% CI, 4 to 11 months). The most common adverse events were fatigue, anorexia, anemia, diarrhea, nausea, rigors/chills, leukopenia, fever, and transaminase elevation. Von Hippel-Lindau gene mutations were detected in four (22%) of 18 archival tumor specimens. Conclusion The confirmed response rate for the combination of sorafenib and interferon in advanced renal carcinoma is greater than expected with either interferon or sorafenib alone. The toxicity of this combination is dominated by adverse events common to interferon that limit further development of this regimen.

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