|Ahead of print publication
Extra-abdominal aggressive fibromatosis treated with meloxicam and sorafenib: An encouraging option
Department of Medical Oncology, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey
Department of Medical Oncology, Istanbul Medical Faculty, Istanbul University, Capa, Fatih, 34093 Istanbul
Source of Support: None, Conflict of Interest: None
Objective: Aggressive fibromatosis (AF), also called desmoid tumor, is an uncommon soft-tissue neoplasm. Characteristically, it expands locally without metastatic potential. However, its tendency of relapse after curative resections has been well documented. Effective treatment options have been limited and there is a clear need for novel treatment strategies.
Methods: We used combination therapy including multikinase tyrosine kinase inhibitor for treating AF.
Results: We presented a case of an extra-abdominal AF who was successfully treated with meloxicam and sorafenib combination in our clinic. She tolerated this therapy well with only mild side effects. To our knowledge, this is the first case report of an extra-abdominal AF with a major partial response to sorafenib and meloxicam combination.
Conclusion: Due to the favorable toxicity profile of sorafenib and meloxicam, this combination might be an effective treatment option for patients with locally aggressive and inoperable AF.
Keywords: Aggressive fibromatosis, meloxicam, oral tyrosine kinase inhibitor, sorafenib
| > Introduction|| |
Aggressive fibromatosis (AF) is a fibroblastic neoplasm arising from musculoaponeurotic stroma and grows locally without a metastatic potential. It has a high tendency of recurrence even after complete surgical resections. It can cause significant morbidity with major functional loss and even death through the destruction of adjacent vital structures and organs. AF accounts for approximately 0.03% of all neoplasms and <3% of all soft-tissue tumors. Incidence in the general population is 2–4 per million population per year  and arises most commonly in the extremities, abdominal cavity, retroperitoneum, and abdominal wall. Individuals between the ages of 15 and 60 years are the most commonly affected population. It has been seen slightly more common in women than in men. The molecular events that lead to AF formation have been incompletely understood. There is an increasing evidence which points the adenomatous polyposis coli and beta-catenin genes, especially in AF secondary to Gardner's syndrome and sporadic AF. Extra-abdominal AF is a rare benign lesion, but it can markedly grow and invade the surrounding tissues. It may necessitate multiple and debilitating surgical interventions for local control, resulting in significant surgery-related morbidity and even loss of the affected limb occasionally. Considering the benign nature of AF, the main aim of the treatment should be symptom control and improvement of quality of life. Due to its high recurrence rates even with wide surgical resection, different alternative treatment modalities including chemotherapy,, radiotherapy, antiestrogen agents, colchicine, and nonsteroidal anti-inflammatory drugs have been studied so far. Previously, new encouraging data with tyrosine kinase inhibitors (imatinib, pazopanib, and sorafenib) were published.,, Sorafenib is a multikinase tyrosine kinase inhibitor with activity against Raf kinase and several receptor tyrosine kinases, including vascular endothelial growth factor receptor 2, 3, platelet-derived growth factor (PDGF) receptor, FLT3, Ret, and kit. The clinical benefit with the use of sorafenib was seen within 2 weeks in symptomatic patients. Interestingly, the majority of responders had extra-abdominal lesions as opposed to intra-abdominal ones.
| > Case Report|| |
Here, we reported a case of AF treated successfully with sorafenib and meloxicam. In 2018, a 38-year-old female patient with recurrent locally advanced right lower extremity AF was referred to our Medical Oncology Clinic at Istanbul University, Institute of Oncology, for medical treatment. Due to the high risk of surgical morbidity, the patient was not suitable for curative resection. She had severe pain and walking disability due to a mass behind the right leg. She was able to walk with a walker. Her medical history was unremarkable. She was on diclofenac and tramadol medication for pain relief. Magnetic resonance imaging (MRI) showed a contrast-enhancing mass lesion (20 cm × 9 cm in size), extending from the right femur 1/3 proximal diaphyseal region to the 1/3 distal diaphyseal region in the posterior compartment along the biceps femoris, vastus intermedius, and vastus lateralis muscles [Figure 1]. Due to the paucity of effective systemic therapy for AF, we decided to treat our patient with sorafenib and meloxicam (because celecoxib was not available in our country) based on a recently published case report which studied sorafenib and celecoxib. A combination of sorafenib 400 mg and meloxicam 15 mg orally per day was initiated in April 2018. Within 2 weeks of treatment, the lesion became softer and smaller. She had a dramatic improvement in pain, lower extremity edema, and she was able to walk without a walker. After 2 months of treatment, an MRI of the right leg was suggested, and a major decrease in tumor volume (nearly 50%) and increase in tumor necrosis and fibrotic component and loss of T2 signal intensity were detected. The patient reported only Grade 1 skin rash and fatigue. She is still on sorafenib and meloxicam without any adverse effect. Unfortunately, this lesion still is not suitable for curative surgery.
|Figure 1: Imaging studies from our patient before and during combination therapy with meloxicam and sorafenib. Panel A and C show the results of T1 contrast-enhanced and T2 magnetic resonance imaging of the right extremity before treatment with meloxicam and sorafenib, with arrows denoting the enhanced contrasting lesion extending from the 1/3 proximal of the right femur to the lateral epicondyle of femur distally. Panel B and D show the results after 2 months of treatment, with arrows denoting the shrinkage of the tumor and growing fibrotic component and decreasing contrast enhancement|
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Informed consent to publish the case (including publication of images) was obtained from the patient.
| > Discussion|| |
We reported our patient who was operated several times for her recurrent lower extremity AF. She had a major objective response to the treatment with a combination of meloxicam and sorafenib. To the best of our knowledge, this is the first case report of extra-abdominal AF where a major partial response has been achieved with a combination of meloxicam and sorafenib. AF has an unpredictable clinical course which ranges from spontaneous regression to rapid progression requiring urgent treatment decision. Because it lacks metastatic potential, local control using surgery and radiation has traditionally been the mainstay of therapy for these tumors. Nevertheless, there is no evidence-based or widely accepted guidelines for the management of unresectable tumors. Systemic therapy should be integrated into a multidisciplinary approach for selected patients for whom local therapy options may cause unacceptable morbidity. In our case, the patient had severe pain and walking disability due to huge mass effect. She was not eligible for surgery and therefore systemic treatment was initiated. Because angiogenesis, increased production of PDGF, and activation of COX-2 pathways  have all important roles in the growth of AF, we chose a tyrosine kinase inhibitor “sorafenib” and COX-2 inhibitor “meloxicam” for first-line treatment. In 2018, Gounder et al. presented first results of their randomized Phase III trial of sorafenib versus placebo in patients with desmoid tumors or AF. In this trial, the partial response rate (RR) with sorafenib was 33%, with durable responses lasting 2–28 months versus a RR of 21% (duration, 4–17 months) with placebo (P = 0.3). The 1-year progression-free survival (PFS) rates were 87% with sorafenib compared to 43% with placebo. Median PFS was not reached (NR) with sorafenib versus 9.4 months (95% confidence interval [CI]: 5.7, NR) for placebo, hazard ratio 0.14 (95% CI: 0.06, 0.33) (P < 0.0001).
In conclusion, favorable side effect profile of sorafenib and meloxicam combination enabled our patient to maintain this therapy without interruption. However, the optimal duration of therapy is unknown. There is clearly a need for an optimal systemic treatment for this rare and often highly morbid disease.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that her name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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