scholarly journals Clinical Activity of Selpercatinib in RET Mutant Pheochromocytoma-Case Reports

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A994-A994
Author(s):  
Bhavana Konda ◽  
Erminia Massarelli ◽  
Jennifer Wright ◽  
Victoria Soldatenkova ◽  
Roderick Clifton-Bligh
Keyword(s):  
Back Pain ◽  
Disease Progression ◽  
Solid Tumors ◽  
Clinical Benefit ◽  
White Male ◽  
Bone Lesion ◽  
White Female ◽  
Clinical Activity ◽  
Ret Mutation ◽  
History Of

Abstract Activating RET gene alterations have been reported in solid tumors including the rare cancer, pheochromocytoma (PHEO) found sporadically and in familial multiple endocrine neoplasia type 2 (MEN2) syndromes. Selpercatinib is a highly selective and potent small molecule RET kinase inhibitor that has demonstrated marked and durable anti-tumor activity in diverse RET-altered solid tumors. Described are the initial 3 PHEO patients treated with selpercatinib (LIBRETTO-001/NCT03157128). Case 1: 70-year-old white male with MEN2A and a history of medullary thyroid cancer (MTC) and PHEO s/p thyroidectomy and adrenalectomy, received MIBG in 1991 and 2016 due to symptom reoccurrence. Progressive metastatic disease associated with severe hypertension was treated with Lutate in 2017 and germline RET mutation p.Cys634Phe was confirmed. After developing severe back pain due to a T6 vertebral metastasis, he began selpercatinib treatment. As of Mar 2020, he has a partial response (PR) as assessed by investigator; his back pain resolved, normetanephrine and metanephrine levels decreased, and has ceased alpha and beta blockers. He remains on treatment with only grade 1-2 adverse events, none requiring interruption or dose modification. Case 2: 51-year-old white female with MEN2A and history of MTC and PHEO s/p thyroidectomy and adrenalectomy in 2010. She developed metastatic PHEO in 2013, with multiple bone, omentum, lung, liver, and spleen metastases. Between 2013 and 2018 she was treated with multiple courses of radiation and, additional surgical resections; a PR with sunitinib lasted 13 months followed by temozolomide/capecitabine treatment. A bone lesion biopsy in 2018 confirmed RET C618S mutation and with her disease progression and uncontrolled bone pain, she began selpercatinib treatment, experiencing a PR. After 5.5 months in the study, she discontinued treatment due to disease progression. Case 3: 45-year-old African American female diagnosed with sporadic PHEO in 1996, s/p multiple surgical resections. She received 2 cycles of cyclophosphamide/vincristine/dacarbazine without clinical benefit. I-131-MIBG therapy with autologous stem cell rescue in 2017 improved blood pressure, palpitations, and flushing but without tumor shrinkage while abdominal pain persisted. Somatic M918T RET-mutation was confirmed, and she began selpercatinib treatment in 2018 with symptom resolution and improved plasma metanephrine levels. She required dose reduction for grade 3 palmar-plantar erthrodysesthesia and had stable disease for 22 months until a new bone metastasis was identified. Due to ongoing clinical benefit, she remains on treatment despite disease progression. Conclusion: These are the initial reports of RET-mutant PHEO patients treated with selpercatinib adding to the diversity of RET-altered tumor types that may benefit from a selective RET inhibitor.

Selinexor in combination with weekly paclitaxel in patients with advanced or metastatic solid tumors: Results of an open label, single-center, multiarm phase 1b study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5565-5565
Author(s):  
Shannon Neville Westin ◽  
Siqing Fu ◽  
Apostolia Maria Tsimberidou ◽  
Sarina Anne Anne Piha-Paul ◽  
Fechukwu Akhmedzhanov ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Solid Tumors ◽  
Clinical Benefit ◽  
Nuclear Export ◽  
Nuclear Accumulation ◽  
Weekly Paclitaxel ◽  
Clinical Activity ◽  
Single Center ◽  
Open Label ◽  
Phase 1B

5565 Background: Selinexor is a first-in-class novel, oral potent selective inhibitor of nuclear export (SINE) which blocks Exportin-1 (XPO1) leading to nuclear accumulation and activation of tumor suppressor proteins and prevention of translation of proto-oncogenes. Weekly paclitaxel is a standard chemotherapy regimen used in various tumor types. Preclinical models show that selinexor with paclitaxel exerts antitumor activity against multiple solid tumors. Our objective was to determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of selinexor and weekly paclitaxel. Methods: This was an open label, single-center, multi-arm phase 1b study utilizing a “3 + 3” design and a “basket type” expansion. Selinexor (twice weekly orally) and weekly paclitaxel (80mg IV 2 week on, 1 week off) was employed as one of 13 parallel arms. Two dose levels (DL) of selinexor were explored: DL1 selinexor 60mg; DL2 selinexor 80mg. Patients (pts) with advanced or metastatic solid tumors were eligible if they had adequate bone marrow and organ function. There was no limit on prior lines of therapy. Efficacy was evaluated using RECIST 1.1. Progression free survival (PFS) was defined as time from treatment until disease progression or death. Results: Of 35 pts treated, all were evaluable for toxicity, and 31 (88%) were evaluable for response. Pt diagnoses included ovarian (n = 28), breast (n = 4), prostate (n = 2), and cervical (n = 1) cancer. Pts had a median of four prior therapies (range 1-10), and 47% had a prior taxane. All pts with ovarian cancer had platinum resistant/refractory disease; high grade serous histology was most common. There were no DLTs and DL1 was chosen as the RP2D given its long term tolerability. 97% of pts had at least one treatment-emergent adverse event (TEAE) and the most common TEAEs were anemia (74%), nausea (57%), fatigue (51%), leukopenia (51%), neutropenia (49%), thrombocytopenia (46%), and vomiting (31%). The most prevalent grade ≥ 3 TEAE were neutropenia (46%), anemia (31%), leukopenia (17%), and fatigue (9 %). Partial responses (PR) were noted in 4 pts (13%); 10 pts (32%) achieved stable disease for > 4 months for a clinical benefit rate (CBR) of 45%. 16 pts (47%) had prior exposure to a taxane, including 1 pt who achieved PR. Among 24 evaluable pts with ovarian cancer, response rate was 17%, CBR was 58%, and PFS was 6.83 months (95% CI 3.73, not reached (NR)). Median duration of clinical benefit in ovarian cancer was 7.57 months (95% CI: 4.43, NR). Conclusions: Oral selinexor in combination with weekly paclitaxel demonstrated promising clinical activity with manageable toxicity, and further evaluation with once weekly selinexor is warranted. This combination should be considered for further exploration in a randomized study, especially in ovarian malignancies. Clinical trial information: NCT02419495.

Effect of zoledronic acid (Zol) compared with placebo on overall disease and bone lesion progression in patients (pts) with bone metastases from certain solid tumors: Stratification by baseline characteristics

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 18541-18541
Author(s):  
K. Ucar ◽  
N. S. Tchekmedyian ◽  
N. Shrina ◽  
Y. Chen ◽  
T. Xie ◽  
...  
Keyword(s):  
Bone Metastases ◽  
Disease Progression ◽  
Pain Score ◽  
Solid Tumors ◽  
Median Time ◽  
Bone Lesion ◽  
Cox Proportional Hazards Model ◽  
Antitumor Effects ◽  
Wide Range ◽  
Baseline Characteristics

18541 Background: Zol has been shown to significantly reduce the risk of skeletal complications compared with placebo in pts with bone metastases from a wide range of solid tumors including a delay of bone lesion progression in pts with renal cancer. To assess whether Zol may reduce the risk of overall disease or bone lesion progression in pts with solid tumors other than breast, non-small cell lung, and prostate cancers, we conducted a retrospective analysis of pts enrolled in a large, randomized, controlled trial. Methods: Pts treated with Zol or placebo were retrospectively stratified by baseline characteristics, including Brief Pain Inventory (BPI) composite pain score, time from initial cancer diagnosis to development of bone metastases, and duration of cancer. The relative risk (RR) of disease progression during 25 months on study was analyzed using the Cox proportional hazards model (stratified log rank). Results: Median baseline BPI pain score was 2.75, median time with cancer was 15 months, and median time to development of bone metastases was 8.5 months. In pts with a baseline BPI score ≥ 2.75 (n = 236), Zol treatment significantly reduced the RR of disease progression by 34% (hazard ratio [HR] = 0.657; P = .014) and the RR of bone lesion progression by 32% (HR = 0.680; P = .028) compared with placebo. Additionally, in pts with cancer duration <15 months (n = 193), Zol treatment reduced the RR of disease progression by 45% (HR = 0.547; P = .002) and the RR of bone lesion progression by 40% (HR = 0.605; P = .016) compared with placebo. Similarly, among pts who developed bone metastases < 8.5 months from initial diagnosis of cancer (n = 193), Zol treatment significantly reduced the RR of disease progression by 39% and the RR of bone lesion progression by 48% compared with placebo (HR = 0.611; P = .009 and HR = 0.519; P = .004, respectively). Conclusions: This exploratory analysis suggests that Zol has potential antitumor effects that may reduce the risk of overall disease and bone lesion progression in pts who have higher pain scores and shorter time to development of bone metastases. Prospective studies are needed to confirm this result. [Table: see text]

Cognitive Behavioral Treatment of Panic Disorder in Elderly Adults: Two Case Studies

1996 ◽  
Vol 10 (4) ◽  
pp. 271-280 ◽  
Author(s):  
Jill H. Rathus ◽  
William C. Sanderson
Keyword(s):  
Panic Disorder ◽  
Elderly Patients ◽  
Behavioral Treatment ◽  
White Male ◽  
Panic Attacks ◽  
Cognitive Behavioral ◽  
White Female ◽  
Cognitive Behavioral Treatment ◽  
History Of

Cognitive behavioral treatment (CBT) has been repeatedly proven efficacious in the treatment of panic disorder (PD); however, information about the efficacy of this treatment with geriatric patients is lacking. The current paper outlines treatment course and outcome for two elderly PD patients receiving CBT. J. B. was a 70-year-old White male with a 51-year history of PD; A. B. was a 69-year-old White female with a 25-year history of PD. Diagnoses were made on the basis of the Structured Clinical Interview for DSM-III-R patient version (SCID-P). Both subjects received manual-driven CBT. Four primary treatment components consisted of psychoeducation, cognitive restructuring, breathing retraining, and systematic exposure. Subjects completed symptom measures before and after treatment and at a follow-up evaluation. Results support the efficacy of the treatment for both patients, as panic attacks, fear and avoidance, and general symptomatology were substantially reduced at post- and follow-up assessments. Results are discussed in terms of the utility of CBT with elderly patients and the nuances of treating elderly patients with this treatment procedure.

scholarly journals Disseminated nocardiosis due to Nocardia farcinica: diagnosis by thyroid abscess culture

2005 ◽  
Vol 47 (6) ◽  
pp. 355-358 ◽  
Author(s):  
Cecília Bittencourt Severo ◽  
Flávio de Mattos Oliveira ◽  
Lenine Cunha ◽  
Vlademir Cantarelli ◽  
Luiz Carlos Severo
Keyword(s):  
Low Back Pain ◽  
Back Pain ◽  
White Male ◽  
Blood Cultures ◽  
Low Back ◽  
Nocardia Farcinica ◽  
Thyroid Abscess ◽  
Days Of Therapy ◽  
History Of ◽  
Disseminated Nocardiosis

A previously healthy 75-year-old white male dentist presented with a 6-month history of low-back pain treated with chronic steroid therapy had a Nocardia farcinica infection diagnosed by aspirate of thyroid abscess and six blood cultures. Despite the treatment with parenteral combination of trimethoprim/sulfamethoxazole, the patient failed to respond and died after two days of therapy. Autopsy revealed disseminated nocardiosis, involving lungs with pleural purulent exudate in both sides, heart, thyroid, kidneys, brain, bones, and lumbosacral soft tissue with destruction of L2-L4.

scholarly journals Clinical Outcomes With Abemaciclib After Prior CDK4/6 Inhibitor Progression in Breast Cancer: A Multicenter Experience

2021 ◽  
pp. 1-8
Author(s):  
Seth A. Wander ◽  
Hyo S. Han ◽  
Mark L. Zangardi ◽  
Andrzej Niemierko ◽  
Veronica Mariotti ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Disease Progression ◽  
Clinical Benefit ◽  
Metastatic Breast ◽  
Predictive Biomarkers ◽  
The United States ◽  
Cross Resistance ◽  
Clinical Activity ◽  
Rapid Progression ◽  
Duration Of Treatment

Background: Inhibitors of cyclin-dependent kinases 4 and 6 (CDK4/6i) are widely used as first-line therapy for hormone receptor–positive metastatic breast cancer (HR+ MBC). Although abemaciclib monotherapy is also FDA-approved for treatment of disease progression on endocrine therapy, there is limited insight into the clinical activity of abemaciclib after progression on prior CDK4/6i. Patients and Methods: We identified patients with HR+ MBC from 6 cancer centers in the United States who received abemaciclib after disease progression on prior CDK4/6i, and abstracted clinical features, outcomes, toxicity, and predictive biomarkers. Results: In the multicenter cohort, abemaciclib was well tolerated after a prior course of CDK4/6i (palbociclib)-based therapy; a minority of patients discontinued abemaciclib because of toxicity without progression (9.2%). After progression on palbociclib, most patients (71.3%) received nonsequential therapy with abemaciclib (with ≥1 intervening non-CDK4/6i regimens), with most receiving abemaciclib with an antiestrogen agent (fulvestrant, 47.1%; aromatase inhibitor, 27.6%), and the remainder receiving abemaciclib monotherapy (19.5%). Median progression-free survival for abemaciclib in this population was 5.3 months and median overall survival was 17.2 months, notably similar to results obtained in the MONARCH-1 study of abemaciclib monotherapy in heavily pretreated HR+/HER2-negative CDK4/6i-naïve patients. A total of 36.8% of patients received abemaciclib for ≥6 months. There was no relationship between the duration of clinical benefit while on palbociclib and the subsequent duration of treatment with abemaciclib. RB1, ERBB2, and CCNE1 alterations were noted among patients with rapid progression on abemaciclib. Conclusions: A subset of patients with HR+ MBC continue to derive clinical benefit from abemaciclib after progression on prior palbociclib. These results highlight the need for future studies to confirm molecular predictors of cross-resistance to CDK4/6i therapy and to better characterize the utility of abemaciclib after disease progression on prior CDK4/6i.

scholarly journals "Hot-water epilepsy ", "warm-water epilepsy", or bathing epilepsy? Report of three cases and considerations regarding an old theme

2005 ◽  
Vol 63 (2b) ◽  
pp. 399-401 ◽  
Author(s):  
Pedro A. Kowacs ◽  
Ivo J.M. Marchioro ◽  
Erasmo B. da Silva Jr ◽  
Samanta F. Blattes da Rocha ◽  
Cristiane A. Simão ◽  
...  
Keyword(s):  
White Male ◽  
Hot Water ◽  
White Female ◽  
Familial History ◽  
Cutaneous Stimulation ◽  
Tactile Stimuli ◽  
Reflex Seizures ◽  
Relevant Role ◽  
History Of ◽  
History Of Epilepsy

Partial and generalized tonic-clonic reflex seizures related to hot water bathing have been described as temperature-related. We describe three cases of bathing epilepsy: a 28 year-old white male and a 30 year-old white female with spells triggered either by warm or hot water, and a 32 year-old female with spells triggered by hot water. The later two of the three cases presented localized epilepsy and a familial history of epilepsy. A complex tactile stimuli might play the most relevant role on seizure triggering, as well as water temperature with an additive effect over cutaneous stimulation.

Erlotinib has activity in androgen-independent prostate cancer (AIPC) patients who are chemotherapy-naive: A phase II trial

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15606-15606 ◽  
Author(s):  
C. Nabhan ◽  
K. Tolzien ◽  
S. Newman ◽  
S. Kelby ◽  
T. Lestingi ◽  
...  
Keyword(s):  
Disease Progression ◽  
Phase Ii ◽  
Stable Disease ◽  
Clinical Benefit ◽  
Single Agent ◽  
Growth Factor Receptor ◽  
Response Assessment ◽  
Complete Response ◽  
Clinical Activity ◽  
Study Results

15606 Background: Mechanisms of hormone resistance for AIPC are variable. One proposed mechanism is the over expression of the epidermal growth factor receptor (EGFR) which in turn stimulates proliferation through its pathway. We aimed to determine the efficacy of an oral anti-EGFR inhibitor (erlotinib) in this patient population that was chemotherapy-naive. The primary end point was to evaluate the overall clinical benefit defined as the sum of complete response (CR), partial response (PR), and stable disease (SD). Methods: Between January and December 2006, sixteen patients were enrolled onto this phase II study. Median age was 78 years (66–85). Median PSA was 61.9 (9.2–800.2). Median time from initial diagnosis until starting Erlotinib was 7.8 years. Erlotinib was given daily at 150 mg until disease progression. Patients were evaluated every 2 weeks for toxicity. Response assessment took place every 2 cycles (each cycle was 4 weeks). Evaluations included computed tomography of measurable disease areas, bone scans, and serum PSAs. Patients who progressed radiographically but maintained a PSA response or those who progressed biochemically but maintained a radiographic response were considered stable and were allowed to continue on study. Results: Sixteen patients were enrolled with 14 being evaluable at this time (2 patients are early in their course). Median cycles received is 2 (range 1.5–12). One patient achieved a PR and continues on Erlotinib after one year of enrollment. Three patients demonstrated stable disease but two of them later progressed. One patient withdrew after 9 days of starting therapy due to fatigue and poor taste. All other patients developed disease progression after two cycles of therapy. The calculated overall clinical benefit was 28% (4 responses out of 14 patients). One patient died from pneumonia and seizures unrelated to Erlotinib as confirmed by an autopsy that showed progression in the central nervous system. Erlotinib was well-tolerated with skin rash and diarrhea being the most common toxicities. Conclusions: Erlotinib has clinical activity as a single agent in AIPC. Updated results of this ongoing study will be presented at the meeting. Further studies with this agent alone or in combination are warranted. No significant financial relationships to disclose.

Celecoxib-Associated Anaphylaxis

2009 ◽  
Vol 43 (4) ◽  
pp. 777-781 ◽  
Author(s):  
Kevin W Chamberlin ◽  
Adam R Silverman
Keyword(s):  
Back Pain ◽  
Immunoglobulin E ◽  
Case Reports ◽  
White Male ◽  
Stable Condition ◽  
Sulfonamide Antibiotics ◽  
Pilonidal Cyst ◽  
First Case ◽  
Bee Sting ◽  
History Of

Objective: To report and discuss a case of anaphylaxis in a young, healthy white male taking celecoxib for intermittent lower back pain. Case Summary: A healthy 27-year-old man with a documented history of anaphylaxis to penicillins and macrolides presented to the emergency department (ED) in anaphylactic shock after ingesting a 200-mg capsule of celecoxib and a cup of orange juice. The patient had been taking celecoxib over the past 6 months, for 1-2 weeks at a time, for low back pain secondary to a pilonidal cyst and an L5/S1 bulging disc. The day of admission was the seventh day of the most recent course of twice-daily celecoxib. The patient initially self-treated the reaction with diphenhydramine and subcutaneous epinephrine that he had at home due to his history of drug- and bee sting-induced anaphylaxis; neither intervention improved his symptoms, He became profoundly diaphoretic and developed systemic swelling, shortness of breath, bradycardia, and hypotension. Emergency medical services transported the patient to the ED, where he was treated appropriately and the symptoms resolved. However, 4 hours later, at time of discharge from the ED, the symptoms recurred. He was admitted to the intensive care unit and monitored for 3 days. Supportive care, steroids, and histamine blockade provided resolution of the symptoms. Cardiac workup was initiated because of the recunence and severity of bradycardia and hypotension; results of the workup were unremarkable. The patient was discharged in stable condition. Discussion: This case demonstrates rare anaphylaxis to celecoxib in a patient who had previously taken the drug and who had documented tolerance to sulfonamide antibiotics. Despite this history, our patient developed type V immunoglobulin E-mediated anaphylaxis secondary to the sulfonamide component of celecoxib. This reaction was considered probable according to the Naranjo probability scale. A review of published case reports and related atlergy literature for celecoxib allergenicity revealed that such reactions are rare. This is the first case report with great detail of a patient with anaphylaxis to celecoxib after having previously tolerated the medication. Conclusions: Celecoxib can produce an anaphylactic reaction in patients who have previously tolerated sulfonamide antibiotics and who have previously tolerated celecoxib. This case also reviews the potentially biphasic presentation of anaphylaxis. Clinicians need to be aware of this biphasic anaphylactic response to ensure optimal duration of evaluation.

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