1. CHEMOTHERAPY FOR PRIMARY HEPATIC MALIGNANCIES Maria Poulou, Eleni Makropoulou, Evangelos Repassos, Emanuel Xydakis, Maria Papadakou, Gerasimos Panagos Department of Medical Oncology Agii Anargiri Cancer Hospital of Kifisia Athens, Greece

2. The prognosis for stage IV primary tumors of the liver is poor and no surgical treatment is recommended Although there were initial encouraging reports of single-agent doxorubicin therapy for hepatocellular carcinoma in Uganda, subsequent studies have failed to confirm the early enthusiastic reports for this or any other single agent The consensus is that no single agent or combination of agents given systemically reproducibly leads to greater than 25% response rates or has any effect on survival

3. Based on review of published studies of chemotherapy, there is no consensus as to the best agent or regimen for unresectable or metastatic cholangiocarcinoma Due to the rarity of the disease, randomized studies have not been conducted In addition, a significant number of patients present with biliary obstruction and elevated levels on liver function tests, which severely curtails the ability to administer chemotherapy

4. Patient population Seventeen patients with primary hepatic malignancies studied retrospectively for their response to chemotherapy Histology was hepatocellular carcinoma in 11 and cholangiocarcima in 6 Disease stage was IVA in 10 and IVB in 7 A1-fetoprotein was high in 6 cases while CA 19-9 in 7 Male:female ratio was 12:5 Median age was 63 (42 to 75, average 61).

5. Treatment All patients received at least 1 cycle of chemotherapy Twelve patients received doxorubicin based chemotherapy as first line treatment while 5 cisplatin based

6. Characteristics, treatments and response to treatment of the hepatocellular carcinoma patients Male/Female8/3 ECOG P.S. 0-2/>23/8 Average age (range)63 (48–75) Stage IVA/VIB6/5 Increased A1Fetoprotein/CA 19-96/2 L.Dox/Dox/L.Dox+FU+Tam/cPla+FU+L/cPla+Ctx7/1/1/1/1 CR/SD+TMd/SD/SD+TMi/PD/PD+TMi1/2/1/1/2/4 2nd line of treatment3 3rd line of treatment/4th line of treatment2/1 Average Overall Survival (range)11 (1–48)

7. Characteristics, treatments and response to treatment of the cholangiocarcinoma patients Male/Female4/24/2 ECOG P.S. 0-2/>23/3 Average age (range)58 (42–68) Stage IVA/VIB4/2 Increased CA 19-95 L.Dox/cPla+FU+L/cPla+FU+L+VP3/1/2 ObjR+TMd/TMd/PD1/1/4 2nd line of treatment4 3rd line of treatment/4th line of treatment1/1 Average Overall Survival (range)14 (5–21)

8. Four patients are still alive and continuing treatment Median overall survival is 11 months (1 to 48+, standard deviation 9.8) Stage IVA and quick tumor marker regression after treatment are good prognostic factors Histology and histologic grading do not seem to possess prognostic significance Both doxorubicin and cisplatin based chemotherapy give objective responses while it seems unlikely for cross resistance to exist