Survival results among patients with alpha-fetoprotein-positive, unresectable hepatocellular carcinoma: analysis of three sequential treatments of the RTOG and Johns Hopkins Oncology Center.
OBJECTIVE
To analyze the observed therapeutic impact of the post-induction components of three treatment programs utilized sequentially between 1983 and 1991 for patients with unresectable alpha-fetoprotein-positive hepatoma.


METHODS
Over a 7.5-year period, three treatment regimens were sequentially utilized: (1) RTOG 83-19, (2) a Johns Hopkins Oncology Center Institutional Pilot Program, and (3) RTOG 88-23. Each treatment program began with an induction phase of external-beam hepatic irradiation (2100 cGy/7 fractions), with concurrent doses of intravenous chemotherapy intended to be radiosensitizing. After induction, patients received cycles of one of the following: (1) intravenous doxorubicin and 5-fluorouracil (5-FU) with or without 131I-polyclonal antiferritin (RTOG 83-19); (2) intrahepatic artery cisplatin (Hopkins Institutional Pilot); or (3) intrahepatic artery cisplatin with or without 131I-polyclonal antiferritin (RTOG 88-23). Analysis of survival results was performed with multivariate and Cox regression methods.


RESULTS
The addition of intravenous 131I-polyclonal antiferritin to post-induction cycles of either intravenous doxorubicin and 5-FU or intrahepatic artery cisplatin did not enhance survival. Intrahepatic artery cisplatin treatment yielded median survival duration of 9.1 months and survival at 12 and 24 months of 37% and 9%, respectively. These results were significantly superior to those resulting from use of intravenous doxorubicin and 5-FU (P = 0.0001; median survival duration 3.6 months; 12- and 24-month survival results 17% and 4%, respectively). A significant survival difference for the cisplatin regimen remained even when patients were stratified by previously identified prognostic factors and the results were appropriately adjusted.


CONCLUSIONS
Patients with unresectable alpha-fetoprotein-positive hepatocellular carcinoma experienced improved survival and decreased toxicity when managed with post-induction cycles of intra-arterial cisplatin as compared with intravenous doxorubicin and 5-FU. Intravenous 131I-polyclonal antiferritin did not improve survival when added to either post-induction regimen but dramatically increased hematologic toxicities.
Abrams
R A
RA
Johns Hopkins Oncology Center, Baltimore, Maryland 21287-8922, USA.
Pajak
T F
TF
Haulk
T L
TL
Flam
M
M
Asbell
S O
SO
D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000532:radiotherapy* / Q000601:surgery; D002945:Cisplatin / Q000009:adverse effects / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010865:Pilot Projects; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome; D000509:alpha-Fetoproteins / Q000032:analysis*
D000970:Antineoplastic Agents; D007457:Iodine Radioisotopes; D000509:alpha-Fetoproteins; D004317:Doxorubicin; D002945:Cisplatin; D005472:Fluorouracil