Extended Progression-Free Survival of Renal Cell Carcinoma with Axitinib: Case Report
Rene A. Muñoz¹, María C. Cabezas²,³*, José Antonio Castillo¹, Camila Miño²,³, Adelin Albert4
¹Hospital Oncológico Solca, Quito General Eloy Alfaro
Avenue 5394, Ecuador
²Pontificia Universidad Católica del Ecuador, Vicente Ramón Roca, Ecuador
³Health & Research Services, Amazonas River Avenue
and Cristobal Colon, Ecuador
4University Hospital Liège, Avenue de l’Hôpital, Liège, Belgium
*Corresponding author: María C. Cabezas, Pontificia Universidad Católica del Ecuador. Amazonas River Avenue and Cristobal Colon, EC170524, Ecuador. Tel: +59324532645; Fax: +593024532645; Email: mariadelcarmencg@yahoo.com
Received Date: 04 July, 2018; Accepted Date: 13 July,
2018; Published Date: 19 July, 2018
Citation: Muñoz RA, Cabezas MC, Miño C, Albert A, Castillo JA (2018) Extended Progression-Free Survival of Renal Cell Carcinoma with Axitinib: Case Report. J Urol Ren Dis 2018: 1102. DOI: 10.29011/2575-7903.001102
1. Abstract
Axitinib is a selective inhibitor of vascular
endothelial growth factor receptors approved for second line treatment of
advanced renal cell carcinoma. The case report concerns an 85-year-old man with
renal cell carcinoma of clear cells initially treated by left nephrectomy who presented
with pulmonary progression 7 years later. Systemic treatment with pazopanib was
initiated but disease progression and gastrointestinal toxicity were observed
after 4 months. A second line treatment implemented with axitinib (5 mg twice
daily, later reduced to 5 mg once daily due to gastrointestinal toxicity) led
to favorable outcome and control of pulmonary progression. This case report demonstrates
that axitinib in reduced dose can improve progression free survival (34 months at
present) and surpass data published in Phase III clinical trials on patients with
localized renal cell carcinoma of clear cells. It further contributes to the
limited information currently available on axitinib in Latin-American
populations.
Keywords: Kidney Cancer; Metastatic Renal Carcinoma; Tyrosine
Kinase Inhibitors
1. Abbreviations
CT : Computer Tomography
ECOG : Eastern
Cooperative Oncology Group
NCCN : National
Comprehensive Cancer Network
OS : Overall Survival
PFS : Progression Free
Survival
RCC : Renal Cell
Carcinoma
RECIST 1.1 : Response Evaluation
Criteria in Solid Tumors
VEGFR : Vascular Endothelial Growth Factor Receptors
2. Introduction
Renal cancer varies greatly from region to region worldwide with an average incidence of 4.4 per 100,000 and a mortality of 1.8 per 100,000 for both genders [1]. In Central and Latin-American countries incidence rates of Renal Cell Carcinoma (RCC) range between 3.0 and 6.8 per 100,000 for men and between 2.5 and 6.4 per 100,000 for women [2]. In Ecuador, the estimated incidence of RCC is 4.2 per 100,000 for men and 3.0 per 100,000 for women [1,2]. Axitinib is a potent anti-angiogenic tyrosine kinase inhibitor approved for the second-line treatment setting in patients with metastatic RCC [3-5]. Two meta-analyses have evidenced a better objective response rate, disease control, progression-free survival (PFS: median 6.7 months) and overall survival (OS: median 20.1 months) after axitinib administration in comparison to sorafenib [6,7]. There is currently very limited information available on the use of axitinib in Latin-American populations compared to other regions. The present case report describes a patient with RCC and distant metastases to the lung, first treated with radical nephrectomy and pazopanib and thereafter, at time of progression, successfully controlled by axitinib in reduced dose with an extended PFS.
3. Case Report
In November 2006, a 75-year-old man underwent a radical left nephrectomy consecutive to RCC incidentally detected by Computer Tomography (CT) scan. The patient had a medical history of splenectomy, due to a left renal retroperitoneal tumor, and pulmonary hypertension with bi-auricular severe dilatation for unknown reasons. No significant family history was reported. The patient had only routine clinical follow-up until December 2013 when he presented fever. Physical examination and laboratory data were normal, but an 11.5 cm left lung mass in the inferior left lobe was evidenced by CT scan. The RCC-related pulmonary metastasis was confirmed by biopsy some days later. Systemic treatment was initiated immediately with oral pazopanib at a daily dose of 400 mg until March 2014 when the drug was suspended due to diarrheic stools grade IV that compromised his life. Six months later, the patient started a second line therapy with axitinib at an oral dose of 5 mg twice a day, dose adjustments based on individual safety and tolerability. Axitinib was swallowed whole with a glass of water. The treatment was carried out according to the National Comprehensive Cancer Network (NCCN) recommendations and National Health Service policies. However, after one month the dose had to be reduced to a single daily dose of 5 mg due to gastrointestinal toxicity grade II (4-6 diarrheic stools per day). Moreover, in October 2014, the patient was transferred to our oncology clinic where medical imaging examinations, laboratory and histopathology tests were performed for a comprehensive management and control. Laboratory data were normal, but the physical examination showed hypophonetic heart sounds with systolic murmur grade 2 in aortic focus, significant edema in both lower extremities and signs compatible with pulmonary effusion. CT evidenced a large amount of left pleural effusion, right metastatic pulmonary nodules in segments II (2.2 cm of diameter) and IX (0.7 cm of diameter) plus left lower lobar atelectasis by occupational mass of 13 x 13.3 x 14 cm of diameter compatible with soft tissue (Figure 1).
Two thoracenteses were performed with a drain of 1800
cc of pleural fluid. Pelvic echography reported a benign prostatism grade I
treated with tamsolusin and prophylactic nitrofurantoin and a right renal
nodule of 25 mm on the superior pole with a parapielic cyst without surgical
criteria. Finally, the lamellae histopathological and immune-histochemical review
revealed pulmonary metastases of RCC of clear cells with Fuhrman grade 2. With
regards to baseline outcomes of axitinib therapy 34 months later the patient
experienced a clinical benefit with stable disease according to RECIST 1.1
(Response evaluation criteria in solid tumors) based on CT scan [8] (Figure 2).
Nevertheless, the patient presented complications such as a deep venous thrombosis of the left safena vein treated with clinical treatment, fecal impaction and bladder balloon treated by enema and urinary catheter, respectively, and a multi-infarct disease in brain (bilateral white matter of the supratentorial area) without sequels controlled with levetiracetam. Additionally, he had subclinical asymptomatic hypothyroidism and reported asthenia, somnolence, dyspnea, periungual desquamation, need for supplemental oxygen for at least 16 hours a day, grade I retrolisthesis in C6, spondylosis and generalized osteopenia in the spine. At present, the 85-year-old patient continues with axitinib (dose of 5 mg orally daily) and has an OS of more than 10.5 years since RCC diagnosis and a PFS of 34 months with an ECOG (Eastern Cooperative Oncology Group) performance index equal to 1 and a Karnofsky score of 90%.
4. Discussion
Cancer of the kidney and renal pelvis represents the sixth
most common cancer in men worldwide [2]. Although
metastatic cancers are traditionally associated with an overall poor prognosis,
axitinib is a potential therapeutic option to consider in advanced RCC [3]. In the latest clinical guidelines, systemic
treatment with tyrosine kinase inhibitors, such as sunitinib, pazopanib and
axitinib, has been approved as first line therapy for RCC [3-5]. Pazopanib in a phase III trial reported a PFS
of 10.5 months and a better toxicity profile in comparison to sunitinib although
in this case study the patient experienced toxicity after only 4 months of
pazopanib treatment [9]. In turn axitinib is a
potent and selective second-generation inhibitor of Vascular Endothelial Growth
Factor Receptors (VEGFR) that bears a relative potency 50-450 times greater
than the first-generation VEGFR inhibitors [10]. International
guidelines recommend axitinib at doses of 5 mg twice a day for an
anti-neoplastic activity but in our case the dose had to be reduced to 5 mg
once a day [3-5]. Despite the dose reduction our
patient showed a notable therapeutic response with an extended PFS. Axitinib demonstrated
to be a well-tolerated drug, with positive clinical outcomes and no negative
impact on quality of life. Our patient experienced the classical adverse events
reported in clinical trials such as fatigue, hypothyroidism, decrease appetite,
nausea and asthenia [7]. Concomitantly, he
presented with a major episode of fecal impaction and bladder balloon due to
unidentified reasons. This case report which adds to the limited knowledge currently
available about the use of axitinib for RCC in Latin-American populations shows
that a reduced dose treatment regimen with axitinib can be as effective as the recommended
doses and may prolong survival in advanced RCC. This hypothesis requires
confirmation in randomized trials.
Figure 1: CT of October 2014 reported a large amount of left
pleural effusion with an occupational mass of 13 x 13.3 x 14 cm of diameter
compatible with soft tissue.
Figure 2: CT of May 2017 reported a tumor mass of heterogeneous
density with multilobed contours, extends from the pulmonary hilum to the chest
wall and measures 9.6 x 7.2 cm of diameter.
4.
Motzer R, Jonasch E, Agarwal
N, Beard C, Bhayani S (2016) Kidney Cancer. NCCN Clinical Practice Guidelines
in Oncology 2: 4-37.