Received: 6 August 2022

Accepted: 9 September 2022

DOI: 10.1111/1759-7714.14669

CASE REPORT

Pazopanib for treating rhabdomyosarcoma in adult patientswith poor performance status: A case report
Yuuya Nishii | Jun Sasaki| Misa Sudou | Ryo Yano
Reiko Takaki | Takaaki Tokito | Tomoaki Hoshino
Division of Respirology, Neurology, andRheumatology, Department of Internal Medicine,
Kurume University School of Medicine, Kurume,
Japan
Correspondence
Jun Sasaki, Division of Respirology, Neurology,and Rheumatology, Department of Internal
Medicine, Kurume University School of Medicine,67 Asahi-machi, Kurume 830-0011, Japan.
Email: sasaki_jun@med.kurume-u.ac.jp| Saeko Tokisawa|Abstract
Rhabdomyosarcoma (RMS) is a common soft tissue sarcoma usually observed inchildren. However, RMS rarely occurs in adults. The prognosis of adult RMS is poor
and a standard chemotherapy regimen has not yet been established. Herein, we report
the case of a 60-year-old Japanese woman with primary anterior mediastinal alveolar
RMS (T3N0M0, stage III). The tumor increased aggressively despite first-line treatment with doxorubicin (60 mg/m2 every 3 weeks for 1 cycle) and second-line treatment with eribulin (1.4 mg/m2 every 3 weeks for 2 cycles). Although her shortness ofbreath and chest tightness worsened as the tumor compressed her heart and left main
bronchus, and her performance status (PS) decreased to 3, third-line treatment withpazopanib (800 mg once daily) was commenced. The treatment led to suppression oftumor growth and resulted in 4-month progression-free survival. Therefore, in casesof adult RMS, considering pazopanib treatment as an option may be beneficial, evenwith previous ineffective treatments or poor PS.
KEYWORDS
pazopanib, poor performance status, rhabdomyosarcoma, soft tissue sarcoma

INTRODUCTION

CASE REPORT

Rhabdomyosarcoma (RMS) is a type of soft tissue sarcoma(STS), observed mostly in children and rarely in adults. STS
accounts for 1% of all adult cancers.1,2 RMS accounts for
only 3.3% of adult STS.3,4First-line treatment comprises surgery in patients withearly-stage RMS5 and chemotherapy in unresectable cases.
Doxorubicin is a widely accepted first-line therapy;6 however, subsequent treatment strategies have not been standardized and prognosis of RMS is poorer in adults than inchildren.4,7 Pazopanib, a multitargeted tyrosine kinase
inhibitor, primarily targets vascular endothelial growth
factor receptors 1–3, platelet-derived growth factor receptors, fibroblast growth factor receptors, and c-kit. In addition, pazopanib is effective in patients with STS previously
treated with standard chemotherapy regimens.8 Herein,
we report a case of mediastinal RMS treated with pazopanib after undergoing two ineffective regimens of doxorubicin and eribulin.

A 60-year-old Japanese woman experienced hoarseness andwas diagnosed with left-sided recurrent nerve paralysis.
Chest radiography revealed a mediastinal tumor (Figure 1a).
Computed tomography (CT) revealed an anterior mediastinal tumor (size, 6.8  6.0  5.7 cm3) without calcification
or obvious fat components (Figure 2a). Magnetic resonanceimaging revealed tumor signals similar to that of the surrounding muscle tissue on fat-suppression T1-weighted imaging and unevenly high-intensity signals on fat-suppression
T2-weighted imaging. Histopathological examination of aCT-guided biopsy specimen confirmed the diagnosis of amalignant alveolar tumor. The tumor cells were positive forcytokeratin AE1/AE3, vimentin, CD56, myogenin, desmin,
myoD1, and HHF35, and negative for S100, p40, and myoglobin (Figure 3a–c).
Therefore, the patient was diagnosed with RMS(T3N0M0 stage III). However, the tumor had invaded theaorta and was unresectable. She was administered standard

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© 2022 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.
Thorac Cancer. 2022;1–4.

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F I G U R E 1 Chest X-ray images. Images showing (a) the mediastinal tumor at the initial visit to our hospital, (b) one month after the initial visit, and(c) two months after the initial visit, at first-line chemotherapy initiation

F I G U R E 2 Contrast-enhanced chest
computed tomography images. Images
showing the (a) anterior mediastinal tumor
at the initial visit to our hospital and(b) two months after the first visit to ourhospital, at first-line chemotherapy initiation.
(c) Image showing an aggressively increased
tumor at the start of pazopanib treatment.
(d) Image showing tumor size reduction andtumor contrast effect at 3 months after
pazopanib initiation

chemotherapy, doxorubicin (60 mg/m2 every 3 weeks) as afirst-line regimen. On treatment initiation, her performancestatus (PS) was 1. Furthermore, the patient had dyspnea onexertion and chest tightness due to aggressive tumor progression over 2 months after her initial hospital visit(Figures 1b,c and 2b). After one cycle of doxorubicin, hercondition deteriorated and the tumor continued to growrapidly. Although her PS had decreased to 2, she received
second-line therapy with intravenous eribulin (1.4 mg/m2
every 3 weeks). After two cycles of eribulin treatment, thepatient experienced an adverse event (AE) of grade 3 neutropenia. Her dyspnea remarkably worsened. Moreover, theprimary tumor grew further, compressing the heart, left
main bronchus, and pulmonary artery (Figure 2c).
Although her PS further decreased to 3, she received
third-line therapy with pazopanib (800 mg daily). After
pazopanib initiation, her shortness of breath slightlyimproved. Enhanced CT showed a slight decrease in tumor
size and contrast effect inside the tumor (Figure 2d). Furthermore, she experienced no AEs (accordingly, no discontinuation or dose reduction) and was discharged from thehospital. Pazopanib treatment effectively suppressed diseaseprogression for 4 months. However, the disease progressedand she died 7 months after first-line treatment initiation.

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3F I G U R E 3 Histopathological examinations. (a) Hematoxylin and eosin staining revealed mesenchymal tumor cells with hyperchromatic nuclei
proliferated in a solid alveolar pattern. (magnification, 200). (b) Immunostaining revealed that the tumor cells were positive for myogenin (magnification,200), and (c) desmin (magnification, 200)

DISCUSSION
The objective response rate (ORR) and progression-free survival (PFS) are poor in patients with RMS undergoing primary treatment of surgery for early-stage cases or
chemotherapy for unresectable cases. The five-year overall
survival (OS) in adult RMS, including resectable cases, is21%, which is far poorer than that in pediatric RMS.9
Although a combination of vincristine, actinomycin D,
and cyclophosphamide is well established for RMS in children, doxorubicin is a widely accepted first-line therapy for
STS,6 which agrees with the Japanese guidelines. Regarding
second- or later-line therapies for STS, three regimens ofpazopanib, eribulin, and trabectedin have been reported aseffective. However, which treatment supersedes the others
remains unknown. The treatment response varies according
to the histological type of STS, and limited data are available
for RMS due to its rarity. In the present case, although themedian PFS for STS is 5.5 months, first-line doxorubicin
was ineffective as only 1 month of PFS was observed.10
In a randomized phase III trial study comparing eribulin
and dacarbazine for previously treated liposarcoma or leiomyosarcoma, eribulin significantly prolonged the OS. However, nosignificant differences in PFS (2.6 months) and ORR (4%) wereobserved.11 Moreover, a phase II trial conducted in Japan
showed the efficacy of eribulin in liposarcoma and other typesof advanced STS, including two RMS cases (3.9%), with a
median PFS of 4.1 months and ORR of 0%. However, 96% ofpatients experienced grade 3–4 treatment-related AEs, withneutropenia (86%) being the most frequently reported AE.12 In
contrast, in the case reported here, we observed a very short
PFS of only 1 month during second-line treatment with eribulin, suggesting its ineffectiveness in this aggressive form of rare
adult RMS.
In a phase III trial study of pazopanib in patients withmetastatic STS and PS of 0–1, pazopanib significantly prolonged the median PFS compared with that with placebo(4.6 vs. 1.6 months, p < 0.0001), with few AEs above grade
3.8 In the present case, pazopanib treatment suppressed
aggressive tumor growth, without any AEs and contributed
towards 4 months of PFS, despite the ineffectiveness ofprevious treatment and her poor PS (3). Enhanced CT
showed a decrease in tumor size and contrast effect inside
the tumor after treatment with pazopanib. Therefore, weconsidered that the antitumor effects of pazopanib weremainly due to suppression of angiogenesis by targeting vascular endothelial growth factor receptors 1–3.
In conclusion, pazopanib treatment should be considered as a viable treatment option in patients with RMS andpoor PS. Furthermore, we consider this case report to be
helpful in formulating a treatment strategy for extremelyrare cases of adult RMS with poor PS.
CONFLICT OF INTEREST
The authors declare that they have no conflict of interest.
OR CI D
Jun Sasaki

https://orcid.org/0000-0001-7202-2880

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How to cite this article: Nishii Y, Sasaki J, Sudou M,
Yano R, Tokisawa S, Takaki R, et al. Pazopanib fortreating rhabdomyosarcoma in adult patients withpoor performance status: A case report. Thorac
Cancer. 2022. https://doi.org/10.1111/1759-7714.
14669