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Last updated 10/27/02

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Hepatic Arterial Infusion Pump (HAI)

HAI is a technique by which chemotherapy is induced directly into the liver by means of a pump - it is thus a form of "regional chemotherapy". This allows a much higher dose of chemo to be delivered to the liver than would be possible by systemic therapy. Variants of HAI have been around for some time (maybe dating to the late 1970's or early 1980's), however it has not been until recently that success (i.e. improved survival time) has been demonstrated in clinical trials. A good intro to HAI (and its limitations) is this webpage by the University of Illinois at Chicago Hepatic Artery Regional Chemotherapy Pump Program . Another useful introductory website is from Medtronic, a company which manufactures some of the pumps.

Sloan Kettering appears to be the only institution having "hard data" showing effectiveness; as such, HAI is not universally accepted as a treatment for liver metastases. There seem to be many variations of pump and/or chemo and/or infusion schedule which could be used for HAI, apparently MSK has the most experience with this and thus has the "best" results. You don't have to go to MSK to be on their HAI protocol, many oncologists in private practice are using it for their patients.

I think the general impression among HAI critics is that it has a fairly high complication rate when compared to systemic chemotherapy (e.g. infections and other things which can go wrong if the pump is not properly placed by an experienced surgeon), plus the efficacy has not been "proven" in large clinical trials by a direct comparison with "the latest" colon cancer chemos (Camptosar and Oxaliplatin) which have only been on the market for a short time. In their eyes, most of the trials showing increased survival all involved comparisions between HAI and 5-FU/Leucovorin, a regimen known to be inferior to current practice for stage IV colon cancer.

Nonetheless, from the MSK data there does seem to be some evidence that HAI could either (1) improve survival in patients with disease confined to the liver which can be completely removed by surgery, RFA or a combination of the two, or (2) "downstage" patients with inoperable, unablatable tumors in the liver to operable status by shrinking their tumors. The latest results I am aware of may be found online here

ASCO 2002 Regional Treatment of Liver Metastases lecture by Nancy Kemeny for techinical details of the most successful HAI program to date. Specific slides include:


Slide 2 Systemic 5-FU/LV gives 20% survival at 2 years, Camptosar increases to 25%, Oxaliplatin 30%
Slide 6 FUDR gives the best response for HAI
Slide 9 HAI vs Systemic
Slide 25 HAI + Systemic (74 patients) vs Systemic (82 patients): 2 year survival 89% vs 65% (p=.02)
Slide 27 Updated Survival Curves from NEJM: 5 year survival 56% vs 45% (HAI+Syst vs Syst)
Slide 37 Cryosurgery failure
Slide 40 Low TS may respond to 5-FU. Lung mets have high TS, so Camptosar may work better

Conclusion: HAI shows improved survival in stage IV, systemic chemo does not seem to alter survival time much.

Proponents of HAI would argue the MSK results show improved results for patients whose disease is confined to the liver, reducing recurrence for those with no evidence of disease following RFA and/or liver resection. Failure seems to result more from extrahepatic disease showing up later than from recurrence in the liver.

There are usually ongoing clinical trials involving HAI, e.g. see this Phase III Randomized Study . Also see Acurian.com or my Clinical Trials Page for more trial info.
    References

  1. 6/25/01 University of Illinois at Chicago Hepatic Artery Regional Chemotherapy Pump Program Good overview of HAI

  2. 8/4/02 Medtronic HAI Page Pump manufacturer homepage

  3. 10/27/02 ASCO 2002 Regional Treatment of Liver Metastases See Nancy Kemeny Lecture

  4. 10/27/02 Experimental and Unconventional Search on HAI

  5. 10/27/02 Colon Cancer Support Search on HAI

    Technical References

  6. 6/24/01 TITLE: Hepatic arterial infusion of chemotherapy after resection of hepatic metastases from colorectal cancer. AUTHOR: Kemeny N, Huang Y, Cohen AM, Shi W, Conti JA, Brennan MF, Bertino JR, Turnbull AD, Sullivan D, Stockman J, Blumgart LH, Fong Y SOURCE: N Engl J Med; 341(27):2039-48 1999 UI: 20061996 Abstract indicates improved 2 year survival at Sloan Kettering with HAI + Systemic Chemotherapy

  7. 6/24/01 TITLE: Hepatic artery infusion chemotherapy for metastatic colorectal carcinoma. AUTHOR: Koea JB, Kemeny N SOURCE: Semin Surg Oncol; 19(2):125-34 2000 UI: 21010613 Study on patients with unresected metastisis. "a recent investigation utilizing HAI with systemic chemotherapy following hepatic resection demonstrates improved local and systemic disease control and overall survival. This approach offers new promise for the curative treatment of the patients with metastatic colorectal carcinoma". "A number of randomized clinical trials in patients with unresected metastases have demonstrated that HAI is associated with a complete response rate in 5% of patients and partial responses up to 60%. In comparison, systemic chemotherapy is associated with a partial response in 20% of cases"

  8. 6/24/01 TITLE: Hepatic arterial therapy for the treatment of metastatic colorectal cancer. AUTHOR: Kemeny NE SOURCE: Semin Oncol; 27(5 Suppl 10):126-31 2000 UI: 20500539

  9. 6/24/01 TITLE: Randomized Study of Hepatic Arterial Infusion (HAI) and Systemic Chemotherapy (SYS) Versus SYS Alone as Adjuvant Therapy After Resection of Hepatic Metastases from Colorectal Cancer (Meeting abstract). AUTHOR: Kemeny N, Cohen A, Huang Y, Shi W, Blumgart L, Turnbull A, Sullivan D, Stockman J, Fong Y SOURCE: Proc Annu Meet Am Soc Clin Oncol; 18:A1011 1999 UI: 99701007 Conclusion: Adjuvant therapy with HAI + sys (A) after liver resection increased 2-yr survival and hepatic DFS over sys alone (B). Median survival not reached for A, 49 months for B, with a median follow-up time of 50 months. Biliary toxicity was usually reversible. To decrease extrahepatic mets, HAI FUDR + D is being combined with systemic CPT-11.

  10. 6/24/01 TITLE: Phase I/II Study of Escalating Doses of Systemic Irinotecan (CPT-11) with Hepatic Arterial Infusion of Floxuridine (FUDR) and Dexamethasone (D), with or Without Cryosurgery for Patients with Unresectable Hepatic Metastases from Colorectal Cancer (Meeting abstract). AUTHOR: Ron IG, Kemeny NE, Tong B, Sullivan D, Fong Y, Saltz L, Paty P SOURCE: Proc Annu Meet Am Soc Clin Oncol; 18:A908 1999 UI: 99700904 18 patient study. The most common site of extrahepatic metastases is the lungs, where metastases demonstrate a high level of thymidylate synthase (TS). Systemic CPT-11, which is more effective than 5-FU in tumors of high TS levels, would therefore be an appropriate drug to use. The combination of HAI-FUDR + D with systemic CPT-11 may increase response rates in the liver and may also decrease the chance of developing extrahepatic metastases

  11. 6/24/01 TITLE: Hepatic arterial chemotherapy in metastatic colorectal patients. AUTHOR: Kemeny NE, Ron IG SOURCE: Semin Oncol; 26(5):524-35 1999 UI: 99456168

  12. 6/24/01 TITLE: Long-term survival achieved by resection of metastases in the liver and lung in a patient with recurrent colonic cancer: report of a case. AUTHOR: Suzuki M, Kadoyama C, Otsuji M, Sugiura T, Kimura F, Suwa T, Fujisawa T SOURCE: Surg Today; 30(11):1037-40 2000 UI: 20560354 The patient remains alive 14 years after the initial resection of colonic cancer. This case is considered noteworthy because it demonstrates the potential effectiveness of local adjuvant chemotherapy and the possibility of extended survival in a patient who has undergone resection of both hepatic and pulmonary metastases from colonic cancer

  13. 6/24/01 TITLE: Colorectal hepatic metastases: resection, local ablation, and hepatic artery infusion pump are associated with prolonged survival. AUTHOR: Heslin MJ, Medina-Franco H, Parker M, Vickers SM, Aldrete J, Urist MM SOURCE: Arch Surg; 136(3):318-23 2001 UI: 21152645 CONCLUSIONS: Surgical resection should be attempted for hepatic colorectal metastases, as this is associated with prolonged overall survival. Hepatic artery infusion pump insertion seems to prolong overall survival for those with unresectable hepatic metastases, but it is not equal to resection. Aggressive surgical management of patients with hepatic colorectal metastases is safe, may prolong overall survival, and therefore should be considered in all patients with metastases confined to the liver.

  14. 6/24/01 TITLE: Therapeutic approaches to metastasis confined to the liver. AUTHOR: Venook AP, Warren RS SOURCE: Curr Oncol Rep; 3(2):109-15 2001 UI: 21114646 Liver metastases nearly always represent disseminated cancer, and systemic therapies are usually indicated. However, in a minority of patients--some with colorectal cancer, others with selected tumors--management of the hepatic disease may be clinically important and even curative. This review identifies unique patient subgroups and novel treatment approaches that may be indicated in patients with liver metastases.

  15. 6/24/01 TITLE: Hepatic arterial 5-fluorouracil in patients with liver metastases of colorectal cancer: single-centre experience in 145 patients. AUTHOR: van Riel JM, van Groeningen CJ, Albers SH, Cazemier M, Meijer S, Bleichrodt R, van den Berg FG, Pinedo HM, Giaccone G SOURCE: Ann Oncol; 11(12):1563-70 2000 UI: 21073678 CONCLUSIONS: The results of our analysis are in line with previous phase III studies. Extrahepatic disease and i.v. 5-FU-based pretreatment were prognostic for reduced OS. The complication rate of hepatic arterial delivery was worrisome. although, no negative impact on survival could be established. There is a strong need for improvement of hepatic arterial delivery methods before further evaluation of hepatic arteria

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