Early onset recall pneumonitis during targeted therapy with sunitinib

Yuasa, Takeshi; Kitsukawa, Shinichi; Sukegawa, Gen; Yamamoto, Shinya; Kudo, Kazuhiko; Miyazawa, Kazunari; Kozuka, Takuyo; Harada, Sohei; Yonese, Junji

doi:10.1186/1471-2407-13-3

Cited by 26 publications

(9 citation statements)

References 10 publications

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“…Although there are reports of radiation dermatitis, bowel toxicities, and pneumonitis, TKIs are generally well tolerated when delivered with radiation. 2,5,8,18,29 However, the safety and efficacy of concur-rent therapy remains particularly unknown despite a growing utilization of SRS in the mRCC patient population. Several investigators have postulated that TKIs offer an added benefit when delivered concurrently with radiation, extrapolating from preclinical models and the radiobiology of SRS.…”

Section: Discussionmentioning

confidence: 99%

Spine stereotactic radiosurgery with concurrent tyrosine kinase inhibitors for metastatic renal cell carcinoma

Miller

Balagamwala

Angelov

et al. 2016

SPI

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OBJECT Systemic control of metastatic renal cell carcinoma (mRCC) has substantially improved with the development of VEGF, mTOR, and checkpoint inhibitors. The current first-line standard of care is a VEGF tyrosine kinase inhibitor (TKI). In preclinical models, TKIs potentiate the response to radiotherapy. Such improved efficacy may prolong the time to salvage therapies, including whole-brain radiotherapy or second-line systemic therapy. As the prevalence of mRCC has increased, the utilization of spine stereotactic radiosurgery (SRS) has also increased. However, clinical outcomes following concurrent treatment with SRS and TKIs remain largely undefined. The purpose of this investigation was to determine the safety and efficacy of TKIs when delivered concurrently with SRS. The authors hypothesized that first-line TKIs delivered concurrently with SRS significantly increase local control compared with SRS alone or TKIs alone, without increased toxicity. METHODS A retrospective cohort study of patients undergoing spine SRS for mRCC was conducted. Patients undergoing SRS were divided into 4 cohorts: those receiving concurrent first-line TKI therapy (A), systemic therapy–naïve patients (B), and patients who were undergoing SRS with (C) or without (D) concurrent TKI treatment after failure of first-line therapy. A negative control cohort (E) was also included, consisting of patients with spinal metastases managed with TKIs alone. The primary outcome was 12-month local failure, defined as any in-field radiographic progression. Multivariate competing risks regression was used to determine the independent effect of concurrent first-line TKI therapy upon local failure. RESULTS One hundred patients who underwent 151 spine SRS treatments (232 vertebral levels) were included. At the time of SRS, 46% were receiving concurrent TKI therapy. In each SRS cohort, the median prescription dose was 16 Gy in 1 fraction. Patients in Cohort A had the highest burden of epidural disease (96%, p < 0.01). At 12 months, the cumulative incidence of local failure was 4% in Cohort A, compared with 19%–27% in Cohorts B–D and 57% in Cohort E (p < 0.01). Multivariate competing risks regression demonstrated that concurrent first-line TKI treatment (Cohort A) was independently associated with a local control benefit (HR 0.21, p = 0.04). In contrast, patients treated with TKIs alone (Cohort E) experienced an increased rate of local failure (HR 2.43, p = 0.03). No toxicities of Grade 3 or greater occurred following SRS with concurrent TKI treatment, and the incidence of post-SRS vertebral fracture (overall 21%) and pain flare (overall 17%) were similar across cohorts. CONCLUSIONS The prognosis for patients with mRCC has significantly improved with TKIs. The present investigation suggests a local control benefit with the addition of concurrent first-line TKI therapy to spine SRS. These results have implications in the oligometastatic setting and support a body of preclinical radiobiological research.

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Section: Discussionmentioning

confidence: 99%

Spine stereotactic radiosurgery with concurrent tyrosine kinase inhibitors for metastatic renal cell carcinoma

Miller

Balagamwala

Angelov

et al. 2016

SPI

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“…Although interstitial pneumonia was an infrequent occurrence and relatively mild in severity, the phase 1 trial concluded that the combination of the mTOR inhibitor and sunitinib produced a high degree of toxicity requiring dose attenuation of both drugs. In addition, there have been two case reports of radiation‐induced interstitial pneumonia as a recall phenomenon occurring during systemic treatment with sunitinib . Taken together, these findings suggest that the systemic administration of mTOR inhibitors and radiation therapy subclinically induces local and/or diffuse lung damage, which can lead to toxic synergism with sunitinib.…”

Section: Discussionmentioning

confidence: 89%

“…There is only one report of sorafenib‐induced interstitial pneumonia, and no reports of pazopanib‐induced pneumonia. In addition, there are just three reports of sunitinib‐induced interstitial pneumonia, and no reports thus far of sunitinib‐induced interstitial pneumonia after recovery from temsirolimus‐induced interstitial pneumonia. In a phase 1 trial of the mTOR inhibitor, everolimus plus sunitinib, in patients with metastatic RCC, one case (equivalent 5%) of grade 2 interstitial pneumonia was reported .…”

Section: Discussionmentioning

confidence: 99%

Sunitinib‐related interstitial pneumonia after treatment with temsirolimus: A case of possible recall phenomenon

2013

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Abbreviations & AcronymsAbstract: A 55-year-old Japanese man was admitted to Oita University Hospital (Oita, Japan) for pyrexia, malaise and dyspnea, and abnormal shadows on chest radiographs. He had started receiving sunitinib (37.5 mg a day for 3 weeks, followed by a 3-week break before beginning the next dosing cycle) for metastatic renal cell carcinoma after the improvement of temsirolimus-induced interstitial pneumonia. Sunitinib is a multiple tyrosine kinase receptor inhibitor approved for the treatment of metastatic renal cell carcinoma, and the most common clinical adverse effects of sunitinib are diarrhea, mucositis, stomatitis, hypertension, rashes and altered taste. We herein report a rare case of sunitinib-related interstitial pneumonia after treatment with temsirolimus for metastatic renal cell carcinoma. This case suggests the possibility of recall phenomenon of drug-induced pneumonia during the administration of additional chemotherapy.

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“…The literature search identified 1440 unique results, where 47 articles met the inclusion criteria with a total of 807 patients included in the data analysis ( Figure 1 ). 1 , 10 , 11 , 13 , 15 , 18 – 60 Demographics, presenting features, treatment, and survival information were compiled for those patients with known status. The majority of patients were male (75.5%), and the mean age at diagnosis of RCC spine metastasis was 56.7 years.…”

Section: Resultsmentioning

confidence: 99%

The Challenges of Renal Cell Carcinoma Metastatic to the Spine: A Systematic Review of Survival and Treatment

Goodwin

Ahmed

Boone

et al. 2017

Global Spine Journal

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Study Design:Systematic review.Objectives:The objective of this systematic review was to answer 2 key questions: (1) What is the clinical presentation and probability of symptomatic improvement following treatment for patients with renal cell carcinoma (RCC) of the spine? (2) What is the overall survival of patients diagnosed with spinal metastases from RCC?Methods:A literature review was performed to identify articles that reported on survival, clinical outcomes, and/or prognostic factors in the RCC population with spinal metastases from 1986 to 2016.Results:Forty-eight articles (807 patients) were included. The Fuhrman Nuclear Grade has been significantly associated with survival in previous studies but was underpowered in the current study. The Memorial Sloan-Kettering Cancer Center Score (MSKCC/Motzer) was also underpowered in the current study. From the time of spinal metastasis, the mean and median survival for patients with previously diagnosed primary RCC was 8.75 and 11.7 months, respectively, whereas synchronously diagnosed patients (primary RCC and spinal metastasis) had a mean and median survival of 6.75 and 11 months, respectively. Patients with a “low” (0-8), “intermediate” (9-11), or “high” (12-15) revised Tokuhashi score at initial presentation had a median survival of 5.4, 11.7, and 32.9 months, respectively.Conclusion:Patients with either a synchronous or latent diagnosis of RCC survived greater than 6 months from the time of presentation. Initial Furhman grade, Tokuhashi score, and MSKCC/Motzer can be useful tools in informing patient-specific prognosis for those with metastatic RCC of the spine.

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Early onset recall pneumonitis during targeted therapy with sunitinib

Cited by 26 publications

References 10 publications

Spine stereotactic radiosurgery with concurrent tyrosine kinase inhibitors for metastatic renal cell carcinoma

Spine stereotactic radiosurgery with concurrent tyrosine kinase inhibitors for metastatic renal cell carcinoma

Sunitinib‐related interstitial pneumonia after treatment with temsirolimus: A case of possible recall phenomenon

The Challenges of Renal Cell Carcinoma Metastatic to the Spine: A Systematic Review of Survival and Treatment

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