Sorafenib @ Octreotide for advanced Liver Cancer

Adding Octreotide to Sorafenib May Benefit Patients With Advanced Hepatic Cell Carcinoma Who Have Failed Other Therapies: Presented at EASL

By Cameron Johnston

http://www.docguide.com

COPENHAGEN, Denmark -- April 25, 2009 -- The addition of octreotide to sorafenib may offer a synergistic benefit for patients with advanced hepatic cell carcinoma (HCC) who have failed or been nonresponsive to other local therapies, researchers stated here at the 44th Annual Meeting of the European Association for the Study of the Liver (EASL).

According to the investigators, who presented their findings on April 24, the combination therapy could represent a much-needed weapon for treating this select, and difficult to treat, population.

"Octreotide has been used previously as monotherapy in patients with HCC but with little success," Liliana Montella, MD, San Giovanni di Dio Hospital, Naples, Italy, told DocGuide. "When patients fail local therapy, they have few chances of a cure, and generally, a poor prognosis."

Originally, 87 patients with HCC who had previously failed radiofrequency ablation, chemoembolisation, surgery, or chemotherapy, or a combination of these treatments were recruited for the study.

The data presented at the poster presentation covered the first 43 patients, although more than 50 have now been evaluated. The patient cohort included 28 with hepatitis C, 10 with hepatitis B, and 1 with both B and C type disease. Four had disease of unknown etiology.

Patients were treated with sorafenib 800 mg/day for 28 days continuous dosing, followed by 1 week of rest. Octreotide 40 mg was introduced on day 10 of the cycle and given every month thereafter.

The analysis showed 1 partial response (2.3%), as measured by Response Evaluation Criteria in Solid Tumors (RECIST) criteria, but Dr. Montella said this would be higher if the EASL criteria were used.

There were 32 cases of stable disease (74%) and 11 cases of progressive disease (23.7%). Median time to progression was 7.0 months (95% confidence interval [CI], 3.0-10.9 months).

Overall survival, at the time of the analysis was 9.9 months (95% CI, 8.2-11.6 months), but Dr. Montella said this has now increased to more than 10 months with 95% confidence intervals ranging from 8.2-17.0 months.

The most common adverse event was diarrhoea, which occurred in 27.9% of patients (4.6% grade 3). Hand-foot syndrome occurred in 9.3% of patients, and hypertension, abdominal pain, and rectal bleeding occurred in 6.9% of patients.

"I personally think that in this select group of liver cancer patients, octreotide can be a very useful drug," concluded Dr. Montella. "We can combine these 2 drugs together to produce some very interesting results in this population of patients."

[Presentation title: Sorafenib Plus Octreotide in Advanced Hepatocellular Carcinoma: Updated Results of a Multicenter Study. Poster 785]

Presentation Date: Apr 25, 2009

SORAFENIB PLUS OCTREOTIDE IN ADVANCED HEPATOCELLULAR CARCINOMA: UPDATED RESULTS OF A MULTICENTER STUDY

S. Del Prete1, R. Addeo1, M. Caraglia2, L. Maiorino3, V. Montesarchio4, G. Cennamo1, R. Guarrasi1, V. Faiola1, L. Leo5, A. Febbraro6, B. Vincenzi7, C. Savastano8, L. Tarantino9, A. Sabia10, E. Capasso11, G. Palmieri12, A. Giorgio13, M. Bianco14, L. Montella1

1Medical Oncology, 'San Giovanni di Dio' Hospital, Frattaminore, 2Department of Biochemistry and Biophysics, Second University of Naples, 3“San Gennaro” Hospital, 4“Cotugno” Hospital, Naples, 5Piedimonte Matese, Caserta, 6Medical Oncology, Fatebenefratelli, Benevento, 7Medical Oncology Campus Biomedico, Rome, 8Medical Oncology “Ruggi d'Aragona” Hospital, Salerno, 9Hepatology and Interventional Ultrasound Unit, 'San Giovanni di Dio' Hospital, Frattaminore, 10Medical Oncology Unit, “S.Maria della Pietà”, Nola, 11Senology Unit, ASL NA3, Arzano, 12Department of Molecular and Clinical Endocrinology & Oncology, University “Federico II”, 13UO di Ecografia Interventistica IX Divisione, “Cotugno” Hospital, Naples, 14Medical Oncology, ASL NA5, Castellammare di Stabia, Italy

Background and aims: Advanced hepatocellular carcinoma (HCC) not amenable to local therapies has limited chances of cure and has a poor prognosis. Sorafenib is a multikinase inhibitor with proven activity in advanced HCC. Octreotide is already used in this setting with conflicting but usually interesting results. An original schedule with sorafenib and long-acting octreotide was tested in advanced HCC patients enrolled to evaluate safety and activity of this combination.

Methods: Patients with advanced HCC not amenable to local therapies, Child-Pugh A or B, received sorafenib at the dose of 800 mg/day continuous dosing for 28 days followed by one week of rest, and long acting octreotide at the dose of 40 mg monthly administered. Cycles were repeated until progression or unacceptable toxicity. The disease-control rate was defined as the percentage of patients who had a best-response rating of complete response, partial response, or stable disease (according to RECIST criteria) lasting for at least 28 days after the first appearance on the basis of independent radiologic review.

Results: At November 1st, 2008, 87 patients have been screened and 77 have been enrolled. At this date, 43 patients were considered evaluable (sex: 36M/7F; age range: 50-82 years; HCV: 28 pts, HBV: 10 pts, HCV+HBV:1 pt; unknown etiology: 4; Child A/B: 34/9, BCLC B/C:17/26). Sixteen patients out of 43 (37%) were naïve from other therapies, while the remaining had been previously treated with local and/or systemic treatments. We registered 1 partial response (2.3%), 32 stable diseases (74%) and 11 progressions (23.7%). Median time to progression (TTP) was 7.0 months (95% CI, 3.0-10.9 months) while the median overall survival was not yet reached. Mean overall survival was 9.9 months (95% CI, 8.2 to 11.6 months). Treatment was generally well tolerated. Grade 3/4 toxicities observed were diarrhoea and hypertension in 4.6% of treated patients, hand-foot syndrome and proctalgia in 2.3% of patients.

Conclusions: Sorafenib plus octreotide appears a feasible option in advanced HCC patients. In the attempt to improve the results obtained with sorafenib alone, this association deserves further investigations in the context of randomized studies.