Lenalidomide in solid tumors

Segler, Angela; Tsimberidou, Apostolia M.

doi:10.1007/s00280-012-1874-2

Cited by 29 publications

(22 citation statements)

References 68 publications

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“…21 Lenalidomide inhibits growth of many hematologic cell lines 21 and is currently being used in clinical trials to treat various hematologic malignancies and solid tumors. [22][23][24][25] In particular, lenalidomide has shown promise in several studies in patients with NHL (not including CTCL), including in patients with relapsed/refractory disease. [26][27][28][29] Despite the rationale for using lenalidomide in patients with CTCL, data on this treatment approach are lacking.…”

Section: Introductionmentioning

confidence: 99%

Results of an open-label multicenter phase 2 trial of lenalidomide monotherapy in refractory mycosis fungoides and Sézary syndrome

Querfeld

Rosen²,

Guitart

et al. 2014

Blood

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A phase 2 multicenter trial was performed to evaluate single-agent lenalidomide in advanced, refractory mycosis fungoides/Sézary syndrome. Thirty-two patients were enrolled with a median of 6 prior treatment regimens, including a median of 4 systemic therapies. Patients achieved an overall response rate of 28% (9 patients), and all were partial responses. Median overall survival was 43 months, median progression-free survival was 8 months, and median duration of response was 10 months. No grade 4 toxicities occurred. Grade 3 adverse events included fatigue (22%), infection (9%), and leukopenia (3%). Patients were frequently unable to tolerate the 25-mg starting dose of lenalidomide used in other hematologic malignancies due to fatigue, pain, and transient flare reaction (TFR) as a contributory factor. TFR appeared to correlate with clinical response, but the small sample size limited definitive conclusions, and the underlying mechanisms of this reaction are not known. Data from correlative studies on peripheral blood samples suggest that the effects of lenalidomide could be associated with decreased circulating CD25(+) T cells and CD4(+) T-cell numbers. Skin lesions showed a trend for increased CD8, CD25, and FoxP3 expression with decreased CD4:CD8 ratio. In conclusion, lenalidomide monotherapy demonstrated activity in refractory cutaneous T-cell lymphomas, along with acceptable toxicity. This trial was registered at www.clinicaltrials.gov as #NCT00466921.

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Section: Introductionmentioning

confidence: 99%

Results of an open-label multicenter phase 2 trial of lenalidomide monotherapy in refractory mycosis fungoides and Sézary syndrome

Querfeld

Rosen²,

Guitart

et al. 2014

Blood

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“…IMiDs (such as thalidomide and lenalidomide, which are used in multiple myeloma and non-Hodgkin lymphoma) and TKIs (such as imatinib, nilotinib and dasatinib, which are used in chronic myeloid leukemia) have also antiangiogenic properties (3). Among side effects of IMIDs and TKIs, alteration of thyroid function and triggering of thyroid autoimmunity has been reported (4)(5)(6)(7)(8)(9)(10)(11)(12)(13). Side effects on the thyroid caused by head and neck radiotherapy include altered function and development of nodules that are at greater risk of being malignant (14).…”

Section: Introductionmentioning

confidence: 99%

“…Thyroid investigations in patients with hematological disorders have essentially focused on the thyroid complications ensuing from chemotherapy and/or external irradiation (4)(5)(6)(7)(8)(9)(10)14,(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28). Because no study has simultaneously taken care of all clinically relevant thyroid aspects (namely, function, autoimmunity and nodules), we have conducted such a study on hematoncologic patients excluding those who had been treated with external irradiation.…”

Section: Introductionmentioning

confidence: 99%

Thyroid function, autoimmunity and nodules in hematological malignancies

Mondello

Sindoni

Pitini

et al. 2015

Arch. Endocrinol. Metab.

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Objective: Hematological malignancies encompass a large spectrum of disease entities whose treatment by chemo/radiotherapy could lead to thyroid complications. To the best of our knowledge, no study has simultaneously addressed thyroid function, autoimmunity and nodularity. Therefore, we decided to conduct one. Materials and methods: We evaluated 82 Caucasian patients (36 women and 46 men), who were treated at our Oncology division for hematological malignancies (multiple myeloma, chronic myeloid leukemia, chronic lymphatic leukemia, non-Hodgkin lymphoma and polycythemia vera) and compared them with a control group of 104 patients. Patients who had received or were receiving external head/neck radiotherapy were excluded. All oncological patients and control individuals underwent thyroid ultrasonography and thyroid function and autoimmunity tests. Results: A lower prevalence of enlarged thyroid and nodules were found in patients with respect to controls. The rate of thyroid nodules was the highest in multiple myeloma and polycythemia vera, and the lowest in chronic lymphatic leukemia. Non-Hodgkin lymphoma patients had the smallest thyroid nodules while men with multiple myeloma the biggest ones. No patient had hypothyroidism, while 5.6% of patients had subclinical hyperthyroidism. In contrast, within the control group the rates of hypothyroidism and hyperthyroidism, overt and subclinical, were 3.8%, 20.2%, 0% and 0% respectively. Moreover, the overall rate of thyroid autoantibody positiveness in patients was significantly lower than controls. Conclusion: In our experience, we found a significantly lower prevalence of thyroid abnormalities in hematologic patients who underwent chemotherapy, but not radiotherapy, with respect to controls. Arch Endocrinol Metab. 2015;59(3):236-44

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“…[1–3] Recent studies have demonstrated that lenalidomide has activity in a variety of solid tumors, although its efficacy as a single agent is modest. [4] The activity of lenalidomide against solid tumors could be enhanced by combining it with other anti-cancer agents, including other anti-angiogenic drugs. A few studies have indicated that lenalidomide can be safely combined with cytotoxic chemotherapy, with possible synergistic effects.…”

Section: Introductionmentioning

confidence: 99%

Phase I clinical trial of lenalidomide in combination with sorafenib in patients with advanced cancer

et al. 2013

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BACKGROUND Preclinical data have shown that lenalidomide and sorafenib target endothelial cells, inhibiting growth of ocular melanoma cells in a xenograft model. We conducted a Phase I study of lenalidomide and sorafenib in patients with advanced cancer. METHODS During the escalation phase, lenalidomide (days 1–21) and sorafenib (days 1–28) were given orally once daily at the following respective doses: level 1 (10 mg, 200 mg); level 2 (10 mg, 400 mg); level 3 (20 mg, 400 mg); and level 4 (25 mg, 400 mg) (1 cycle = 28 days). A “3+3” study design was used. RESULTS Forty-one patients were treated (median age: 50 years). The most common diagnoses were adenoid cystic carcinoma (N=9), ovarian adenocarcinoma (N=7), and melanoma (N=6); 142 cycles (median: 3) were administered. No dose-limiting toxicities were noted. The maximum tested dose (dose level 4) was used in the expansion phase. Grade 3–4 treatment-related toxicities were neutropenia, thrombocytopenia, skin rash, and thromboembolism. Of 38 patients who were evaluable for response, stable disease (SD) was noted in 53% of patients (SD ≥6 months: 16%). Tumor types with SD≥6 months were as follows: ocular melanoma, 2/2 (100%); other melanoma, 1/4 (25%); adenoid cystic carcinoma, 2/9 (22%); and ovarian cancer, 1/6 (17%). The median progression-free survival duration was 3.5 months (95% CI, 1.9–5.0), and the median overall survival duration was 12.3 months (95% CI, 10.1–14.5). CONCLUSIONS Lenalidomide and sorafenib was well tolerated and associated with disease stabilization for ≥6 months in patients with melanoma, adenoid cystic carcinoma, and ovarian adenocarcinoma.

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Lenalidomide in solid tumors

Cited by 29 publications

References 68 publications

Results of an open-label multicenter phase 2 trial of lenalidomide monotherapy in refractory mycosis fungoides and Sézary syndrome

Results of an open-label multicenter phase 2 trial of lenalidomide monotherapy in refractory mycosis fungoides and Sézary syndrome

Thyroid function, autoimmunity and nodules in hematological malignancies

Phase I clinical trial of lenalidomide in combination with sorafenib in patients with advanced cancer

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