Results of a phase 2/3 open-label, randomized trial of T138067 versus doxorubicin (DOX) in chemotherapy-naïve, unresectable hepatocellular carcinoma (HCC)

Posey, James; Johnson, P. W. M.; Mok, Tony; Hirmand, Mohammad; Dahlberg, Steve; Kwei, Long; Leung, TW

doi:10.1200/jco.2005.23.16_suppl.4035

Cited by 25 publications

(10 citation statements)

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“…Of 339 patients with available data, 169 were randomized to T138067 at a 250-mg/m 2 weekly infusion and 170 were randomized to doxorubicin at a 60-mg/m 2 infusion every 3 weeks. No overall survival difference was seen, with a median survival time of 6 months in each arm [57].…”

Section: Chemotherapymentioning

confidence: 88%

“…This agent inhibits microtubule formation by binding irreversibly and specifically to isotypes of β-tubulin, causing cell arrest at G 2 /M and inducing apoptosis. Based on the initial preclinical and clinical experience of antitumor activity [53][54][55][56], a phase II/III open-label, randomized trial was performed comparing T138067 with doxorubicin in chemotherapy-naïve, unresectable HCC [57]. Unfortunately, that study was closed early after recommendation from the External Data Monitoring Committee because of a lack of survival benefit for T138067.…”

Section: Chemotherapymentioning

confidence: 99%

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Systemic Therapy of Advanced Hepatocellular Carcinoma: How Hopeful Should We Be?

2006

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Worldwide, hepatocellular carcinoma (HCC) is the fifth most common cancer and the third most common cause of cancer-related death. In the U.S., 18,510 new cancers of the liver and intrahepatic bile duct are expected in 2006, with an estimated 16,200 deaths. The incidence rates for HCC in the U.S. continued to rise steadily through 1998 and doubled during the period 1975-1995. Unresectable or metastatic HCC carries a poor prognosis, and systemic therapy with cytotoxic agents provides marginal benefit. A majority of HCC patients (>80%) presents with advanced or unresectable disease. Even for those with resected disease, the recurrence rate can be as high as 50% at 2 years. Because of the poor track record of systemic therapy in HCC, there has been a sense of nihilism for this disease in the oncology community for decades. However, with the arrival of newly developed molecularly targeted agents and the success of some of these agents in other traditionally challenging cancers, like renal cell carcinoma, there has recently been renewed interest in developing systemic therapy for HCC. This review attempts to concisely summarize the historical perspective and the current status of systemic therapy development in HCC. The Oncologist

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Section: Chemotherapymentioning

confidence: 88%

Section: Chemotherapymentioning

confidence: 99%

Systemic Therapy of Advanced Hepatocellular Carcinoma: How Hopeful Should We Be?

2006

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“…In a trial performed in Hong Kong, doxorubicin was compared with PIAF (n = 188) and, while the superior response rate of PIAF was confirmed; 10.5% vs. 20.9%, the difference in survival; 6.8 vs. 8.7 months, was not significant [13]. The b-tubulin binding drug T138067 which inhibits microtubule formation was studied in a large global trial (n = 339) and found to have an almost identical median survival to doxorubicin (5.7 vs. 5.6 months respectively) [15]. This trial remains in abstract form only despite having been presented in 2005.…”

Section: Randomised Trialsmentioning

confidence: 93%

Are there opportunities for chemotherapy in the treatment of hepatocellular cancer?

Asghar

Meyer

2012

Journal of Hepatology

164

138

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Hepatocellular cancer is a significant global health problem yet the prognosis for the majority of patients has not changed significantly over the past few decades. For patients with advanced disease, sorafenib is currently the standard of care providing a survival advantage of 2-3 months in selected patients. Cytotoxic chemotherapy has been used for over 30 years but definite evidence that it prolongs survival has been lacking. Resistance remains a significant barrier for both targeted and cytotoxic agents and an understanding of the underlying mechanisms is critical if outcomes are to be improved. Here, we summarise the past and current data that constitute the evidence base for chemotherapy in HCC, review the causes of chemoresistance and suggest strategies to overcome these barriers.

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“…T138067 binds to the beta-tubulin subunit of alfa/ beta-tubulin, inducing mitotic arrest and apoptosis. Preliminary analysis of a phase 3 trial comparing T138067 with doxorubicin (n=339) in patients with chemotherapy-naïve unresectable HCC has been presented in abstract form 55 and did not demonstrate an improved median overall survival with T138067 (median overall survival 6 months for both treatment arms).…”

Section: Systemic Cytotoxic Chemotherapymentioning

confidence: 98%

Systemic therapy of hepatocellular carcinoma: Are we making progress?

Roxburgh

Evans

2008

Adv Therapy

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Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the third most common cause of cancer deaths. Surgical resection, with or without transplantation, can result in long-term survival. However, surgery can only be performed in about 15% of patients with HCC and the 5-year survival rate is only approximately 33%-50% after potentially curative resection. Percutaneous ethanol injection, radiofrequency ablation, and transarterial chemoembolization are invasive techniques that have shown efficacy in reducing tumor bulk. Similarly, systemic chemotherapy may induce tumor responses, but a survival benefit has not been clearly demonstrated. In addition, the lack of efficacy of antiandrogens, tamoxifen, and single-agent interferon has now been confirmed.Sorafenib is a multikinase inhibitor with antiangiogenic, proapoptotic, and Raf kinase inhibitory activity. In a large, multicenter, randomized, phase 3 trial there was a significant improvement in both time to disease progression and overall survival with sorafenib compared with placebo. Sorafenib is the first agent to demonstrate a consistent improvement in overall survival for patients with advanced HCC. Further studies are required to determine the role of other molecular-targeted therapies, either alone or in combination with sorafenib in patients with advanced HCC. Further studies are also required to determine the role of sorafenib in combination with locoregional therapies (eg, transarterial chemoembolization), and the role of sorafenib as adjuvant therapy following surgery.

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Results of a phase 2/3 open-label, randomized trial of T138067 versus doxorubicin (DOX) in chemotherapy-naïve, unresectable hepatocellular carcinoma (HCC)

Cited by 25 publications

References 0 publications

Systemic Therapy of Advanced Hepatocellular Carcinoma: How Hopeful Should We Be?

Systemic Therapy of Advanced Hepatocellular Carcinoma: How Hopeful Should We Be?

Are there opportunities for chemotherapy in the treatment of hepatocellular cancer?

Systemic therapy of hepatocellular carcinoma: Are we making progress?

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