A Phase II Randomized Dose Escalation Trial of Sorafenib in Patients With Advanced Hepatocellular Carcinoma

Rimassa, Lorenza; Pressiani, Tiziana; Boni, C.; Carnaghi, Carlo; Caremoli, Elena Rota; Fagiuoli, Stefano; Foa, Paolo; Salvagni, Stefania; Cortesi, Enrico; Tronconi, Maria Chiara; Personeni, Nicola; Bozzarelli, Silvia; Banzi, M.; Fanello, Silvia; Lutman, Fabio Romano; Giordano, Laura; Santoro, Armando

doi:10.1634/theoncologist.2012-0221

Cited by 33 publications

(18 citation statements)

References 18 publications

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“…The potential correlation of treatment-emergent AEs during sorafenib therapy has been evaluated in several studies [54][55][56][57][58], and according to the results of a very recent prospective study, the development of dermatologic AEs within 60 days of sorafenib initiation appears associated with better survival [59]. The identification of alternative dosing schedules in some selected cases is a further field of research [45][46]60].…”

Section: Hepatocellular Carcinomamentioning

confidence: 99%

Sorafenib: 10 years after the first pivotal trial

Gadaleta-Caldarola¹,

Infusino²,

Divella

et al. 2015

Future Oncol.

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Sorafenib is an oral multikinase inhibitor with anticancer activity against a wide spectrum of cancers. It is currently approved for the treatment of patients with hepatocellular carcinoma, advanced renal cell carcinoma or progressive, locally advanced or metastatic differentiated thyroid carcinoma. In this review, we present a number of studies that investigated the efficacy and safety of sorafenib in these settings. We also discuss the perspectives on the use of this molecule, including the role of sorafenib as comparator for the development of new drugs, the combination of sorafenib with additional therapies (such as transarterial chemoembolization for hepatocellular carcinoma) and the use of this treatment in several other advanced refractory solid tumors.

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Section: Hepatocellular Carcinomamentioning

confidence: 99%

Sorafenib: 10 years after the first pivotal trial

Gadaleta-Caldarola¹,

Infusino²,

Divella

et al. 2015

Future Oncol.

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“…In a study by Rimassa et al, the strategy of sorafenib dose escalation upon disease progression while on sorafenib failed to demonstrate any improvement in clinical outcome [63]. This prospective study did not meet its primary end point of improved PFS in patients who were escalated to sorafenib 1200 mg/day (n = 49) compared with those who received best supportive care (n = 52) following radiologic disease progression while on sorafenib 800 mg/day; the PFS values were 3.91 vs 2.69 months, respectively (p = 0.086).…”

Section: Treatment Beyond Progressionmentioning

confidence: 99%

Refining Sorafenib Therapy: Lessons from Clinical Practice

et al. 2014

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AbstrAct:Understanding the best use of sorafenib is essential in order to maximize clinical benefit in hepatocellular carcinoma. Based on Phase III and noninterventional study data, as well as our extensive experience, we discuss dose modification in order to manage adverse events, disease response evaluation and how to maximize treatment benefit. Sorafenib should be initiated at the approved dose (400 mg twice daily) and reduced/ interrupted as appropriate in order to manage adverse events. Dose modification should be considered before discontinuation. Appropriate tumor response assessment is critical. Focusing on radiologic response may result in premature sorafenib discontinuation; symptomatic progression should also be considered. If second-line therapies or trials are unavailable, continuing sorafenib beyond radiologic progression may provide a clinical benefit. Our recommendations enable the maximization of treatment duration, and hence clinical benefit, for patients. Keywords:• adverse event managementIt is well established that hepatocellular carcinoma (HCC) is a complex and heterogeneous disease that is affected by multiple genetic and epigenetic alterations [1]. In the overwhelming majority of patients, liver cirrhosis -another complex disease in its own right -is superimposed on HCC. As a result, the prognostic range for these patients varies considerably and continues to change for each patient at every time point over the clinical course of their disease. A meta-analysis of 30 clinical trials into which HCC patients were enrolled for palliative treatment reflects this heterogeneity. It demonstrated a high variability in survival among untreated patients and concluded that no single patient characteristic alone could predict outcome [2].The prognosis and treatment options for HCC are generally related to tumor stage and liver function at presentation [3,4]. In the west, approximately 30% of all patients with HCC are diagnosed in

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“…A prospective phase II trial comparing dose increase of sorafenib after progression to best supportive care showed only a trend towards a prolongation of OS and progression-free survival, but it failed to reach statistical significance [19]. In this trial, however, toxicity due to dose escalation of sorafenib as well as randomization imbalances might have negatively affected the outcome of patients treated beyond progression.…”

Section: Discussionmentioning

confidence: 92%

Survival of Hepatocellular Carcinoma Patients Treated with Sorafenib beyond Progression

Apostolidis

Pfeiffenberger

Gotthardt

et al. 2018

Gastrointest Tumors

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Background/Aim: Sorafenib leads to improved survival in advanced hepatocellular carcinoma (HCC) patients. Continuation of sorafenib beyond progression has been a possible treatment strategy when further approved therapeutic agents are lacking. Methods: We performed a retrospective analysis of all HCC patients at our institution with documented disease progression under treatment with sorafenib. Overall survival (OS) from start of sorafenib treatment was compared between patients who received sorafenib for > 3 weeks beyond progression (group 1) and those who discontinued sorafenib ≤3 weeks after progression (group 2). Group 1 was further subdivided into those patients who received sorafenib for > 3 months (group 1a) and those who received it for ≤3 months (group 1b). Results: A total of 71 patients were analyzed. Median OS for all patients was 15.4 months. OS in group 1 (15.6 months) and 2 (13.0 months) was similar (p = 0.90). Patients in group 1a showed significantly prolonged median OS (19.7 months) compared to that of patients in group 1b (13.6 months, p = 0.004), and they showed a trend towards prolonged OS compared to group 2 (p = 0.126). For patients with a poor prognosis according to their Child-Pugh stage, performance status, alpha-fetoprotein, and response to prior sorafenib treatment, OS was significantly prolonged in group 1 versus group 2 (12.1 vs. 6.4 months, p = 0.019). Conclusion: In HCC patients, continuing sorafenib beyond progression for > 3 months is associated with improved survival compared to discontinuing sorafenib within 3 months. Furthermore, patients with a poor prognosis who continue sorafenib beyond progression in general show significantly prolonged survival.

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A Phase II Randomized Dose Escalation Trial of Sorafenib in Patients With Advanced Hepatocellular Carcinoma

Cited by 33 publications

References 18 publications

Sorafenib: 10 years after the first pivotal trial

Sorafenib: 10 years after the first pivotal trial

Refining Sorafenib Therapy: Lessons from Clinical Practice

Survival of Hepatocellular Carcinoma Patients Treated with Sorafenib beyond Progression

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