Sunitinib adverse events in metastatic renal cell carcinoma: a meta-analysis.

BACKGROUND: Sunitinib, a multi-targeted receptor tyrosine kinase inhibitor, has demonstrated survival benefit in patients with metastatic renal cell carcinoma (mRCC); however, significant adverse events (AEs) have been associated with its use. The significant variation in the reported incidences of AEs has prompted this meta-analysis to quantify the risk and explore associated predictors. METHODS: According to predefined selection criteria, a literature search identified 12 studies that were included in the analyses. RESULTS: The meta-analysis included 5,658 patients; 66 % patients had prior systemic therapy whereas the remaining patients (34 %) received sunitinib in the first-line setting. For any grade toxicity, skin rash, fatigue, diarrhea, and mucositis were the most frequently encountered events (81, 52, 45, and 33 %, respectively). Anemia, neutropenia, or thrombocytopenia of any grade occurred in more than one-third of patients, although grades 3 or 4 were less common. Any grade raised by liver enzymes or serum creatinine occurred in 40 and 44 % of patients, respectively. Meta-regression analyses showed that study size was inversely related to the risk of experiencing fatigue, diarrhea, mucositis, anemia, and thrombocytopenia. In particular, the incidence of AEs was higher when sunitinib was used in pretreated versus naive patients; however, there was no significant difference between the two groups concerning the incidence of laboratory abnormalities. We addressed the limitations of reporting AEs in clinical studies. CONCLUSIONS: The present meta-analysis quantified sunitinib-associated AEs. The derived estimates would be similar to that to be expected from the use of sunitinib in community practice in unselected patients with metastatic renal cell carcinoma (mRCC).

Increased risk of second lung cancer in Hodgkin's lymphoma survivors: a meta-analysis.

BACKGROUND: Patients treated for Hodgkin's lymphoma (HL) have a higher risk of developing second lung cancer (SLC) compared with the general population. The aim of this meta-analysis was to quantify such risk and to analyze contributing risk factors in HL survivors. METHODS: According to predefined selection criteria, a literature search identified 21 studies that were included in the analysis. RESULTS: After eliminating overlapping or duplicate data, 793 (76 % males) incidences of SLC were encountered in 74,831 patients (58 % males) with HL over a median follow-up of 11.5 years. The median age at HL diagnosis and the median age at SLC diagnosis were 33.0 and 45.9, respectively. The mean latency between treatment of HL and development of SLC was 11.5 years. The pooled relative risk (RR) of SLC was 4.62 (95 % confidence interval [CI], 3.18-6.70], I (2) = 98 %), with a median absolute excess rate of 10.4 per 10,000 person-years. RR was positively related to study size, male-to-female ratio, institutional versus population-based data sets, and the use of any radiotherapy (RT) or combined modality therapy (CMT), while age at diagnosis of HL was not significant. The highest risk was shown among patients aged 15-24 years (RR = 8.76 [95 % CI, 4.55-16.89]), while the lowest risk occurred in patients ≥55 years at primary treatment (RR = 2.88 [95 % CI, 2.33-3.56]). RR increased by increasing duration of follow-up, reaching the highest value at 10-14 years (RR = 4.17 [95 % CI, 3.62-8.81]), but did not increase after ≥15 years (RR = 4.01 [95 % CI, 2.68-5.98]). RT only, CMT, or chemotherapy only was associated with RR (95 % CI) of 4.88 (3.14-7.60), 5.15 (4.08-6.50), and 2.39 (1.60-3.55), respectively. Patients with SLC demonstrated poor prognosis. CONCLUSIONS: The current meta-analysis provided a detailed estimate of the risk of SLC among HL survivors. The obtained results may provide guidelines concerning lung cancer screening for this population.

Risk of second breast cancer in female Hodgkin's lymphoma survivors: a meta-analysis.

BACKGROUND: Women treated for Hodgkin's lymphoma (HL) have an elevated risk of developing second breast cancer (SBC) compared with the general population. We planned this meta-analysis to quantify the long-term risk of SBC and analyze the contributing risk factors among HL survivors. METHODS: According to predefined selection criteria, literature search identified 34 studies that were included in the analyses. RESULTS: After eliminating overlapping or duplicate data, 957 incidences of SBC were encountered in 24,505 females with HL over a median follow-up of 14.9 years. The medians: age at the diagnosis of HL, age at diagnosis of SBC, and latency since HL treatment to the development of SBC were 23.7, 35.0, and 17.7 years, respectively. The pooled relative risk (RR) of SBC was 8.23 (95% CI, 5.43-12.47, I² = 96%), with a median absolute excess rate of 22.9 per 10,000 person-years. The RR was found inversely related to age at diagnosis of HL with the highest rate (68.7; [95%CI, 28.08-168.11], I² = 79%), occurred in young patients (≤ 15 years old), where the RR in older women (≥ 40 years old) was not significant (0.55; [95% CI, 0.09-3.52]). Analysis of RR by 5-year increments since the treatment of HL showed that the risk was highest after 15-19 years of latency (13.87; [95% CI, 7.91-24.30], I² = 89%). Analysis of the effect of treatment modalities showed that the RR rates were (4.70; [95% CI, 3.28-6.75], I² = 74%), (5.65; [95%CI, 2.94-10.88], I² = 91%), and (1.19; [95% CI, 0.50-2.82], I2 = 65%), for radiotherapy (RT) only, combined RT and chemotherapy (CT), and CT only, respectively. To investigate the demonstrated heterogeneity, meta-regression analysis was performed when feasible. In most such analyses, the natural logarithm of RR was inversely associated with age at HL diagnosis. CONCLUSIONS: We conclude that, the current meta-analysis provided the most recent comprehensive estimate of the risk of SBC in a broad-range of HL survivors. Younger age at diagnosis proved to be a dominant risk factor. The obtained results would serve providing breast cancer screening recommendations for HL survivors.