Alternating floxuridine and 5-fluorouracil hepatic arterial chemotherapy for colorectal liver metastases minimizes biliary toxicity.

BACKGROUND: The goals of this study of a hepatic arterial infusion (HAI) regimen of alternating floxuridine and 5-fluorouracil were to evaluate the treatment-related toxic effects, the antitumor response rate, and patient survival. METHODS: Fifty-seven consecutive patients were treated with implanted HAI pumps and received a regimen of alternating floxuridine (0.1 mg/kg/day continuous HAI for 7 days) followed by a weekly HAI pump bolus of 5-fluorouracil (15 mg/kg for 3 weeks). Any changes in treatment plan because of toxicity, antitumor response, and survival were recorded. RESULTS: Thirty-one (54.4%) patients responded to this HAI regimen; 14 (24.5% )patients had stable disease, and 12 (21.1%) progressed during treatment. Responders or patients with stable disease had a significantly (P < 0.05) improved survival rate (19 months median) compared with patients in whom disease progressed (12 months median). Two (3.5%) patients developed biliary sclerosis and 12 (21.1%) had mild transient liver function abnormalities. The liver alone or in combination with another area was the site of first progression of disease in 40 (70.2%) patients. CONCLUSIONS: This regimen had reversible or no hepatobiliary toxicity in more than 95% of patients. Tumor reduction or stabilization of disease was observed in 79% of the patients, who had a median survival of 19 months. Reduced toxicity and more effective chemotherapeutic regimens may increase the likelihood of survival after HAI chemotherapy for unresectable colorectal liver metastases.

Adjuvant hepatic arterial infusion chemotherapy after curative resection of colorectal liver metastases.

We performed a prospective study of adjuvant hepatic arterial infusion chemotherapy after resection of colorectal liver metastases. We placed hepatic arterial infusion ports in 20 consecutive patients undergoing curative resection of colorectal liver metastases. The chemotherapy regimen was a weekly bolus of 5-fluorouracil (15 mg/kg) for 6 months. The median follow-up has been 33 months. Nine of the 18 evaluable patients (50%) have developed recurrent colorectal cancer. The liver was the only site of failure in 3 of 18 patients (17%), and extrahepatic recurrences occurred in 6 of 18 patients (33%). All patients without recurrence are alive. The median survival of the patients without recurrent disease is 39 months, compared with 27 months for those with recurrent metastatic disease (p < 0.01). In patients who received adjuvant hepatic arterial infusion chemotherapy compared with historical controls treated with surgery alone, we have observed a decreased incidence of recurrent disease after liver resection for metastases. We recommend that patients who undergo hepatic resection for colorectal metastases be considered for postoperative adjuvant chemotherapy to decrease the likelihood of recurrence and to improve survival.

Technical considerations and complications associated with the placement of 180 implantable hepatic arterial infusion devices.

BACKGROUND: Treatment regimens with hepatic arterial chemotherapy infusion are being investigated in an attempt to improve survival and quality of life for patients with primary and metastatic liver malignancies. The successful delivery of chemotherapeutic drugs through an implantable hepatic arterial infusion device depends on the surgeon's understanding of hepatic arterial anatomy, the proper cannulation technique, and the operative measures necessary to prevent misperfusion of drug. METHODS: Between January 1, 1987, and December 31, 1991, we placed implantable hepatic arterial infusion devices in 180 patients. The records of these patients were review to determine (1) the incidence and surgical management of variant hepatic arterial anatomy and (2) the complications associated with surgical placement of these devices. RESULTS: Variant hepatic arterial anatomy requiring ligation of the variant vessel or nonstandard cannulation was seen in 66 patients (36.7%). Treatment response rates and duration of treatment were no different for these 66 patients than for the 114 patients with standard hepatic arterial anatomy (p = 0.94). There were no operative deaths in this series. Operative or early postoperative (within 30 days) complications occurred in 10 patients (5.5%). However, late complications or device-related malfunctions developed in 52 patients (28.8%). CONCLUSIONS: An understanding of regional arterial anatomy is required to surgically place a catheter to achieve bilobar hepatic arterial perfusion and avoid gastroduodenal misperfusion of drug. Placement of hepatic arterial infusion devices has a low rate of early morbidity, but surgeons should be aware of late complications that may develop in patients undergoing hepatic arterial chemotherapy infusion through an implantable device.

Alternating hepatic intra-arterial floxuridine and fluorouracil: a less toxic regimen for treatment of liver metastases from colorectal cancer.

Hepatic intra-arterial (HIA) infusion of floxuridine (FUDR) via an implanted pump has shown promise in the treatment of colorectal cancer metastasized to the liver. However, the potential benefit of this therapy may be offset by the high incidence of treatment-limiting biliary toxicity. Although weekly HIA bolus of fluorouracil (5-FU) is effective against metastatic colorectal cancer to the liver with no biliary toxicity, it is limited by systemic side effects. In December 1986, we began a phase II trial of alternating HIA FUDR and 5-FU via the implanted pump in an attempt to extend the duration of treatment by obviating the limiting biliary (FUDR) and systemic (5-FU) drug toxic effects. Patients received continuous HIA FUDR at 0.1 mg/kg of body weight per day on days 1 through 8 followed by an HIA bolus of 5-FU at 15 mg/kg given via the pump sideport on days 15, 22, and 29, with the cycle repeated every 35 days. Sixty-eight patients were enrolled in this trial, and 64 were fully evaluable. Of the 64 patients, 30 (47%) previously had received chemotherapy. Major response (complete response plus partial response) was observed in 32 (50%) of 64 patients, and the median survival from pump implantation in all patients was 22.4 months. In contrast to the experience with the single-agent HIA FUDR regimen, no patient had treatment terminated because of drug toxicity. Alternating HIA FUDR and 5-FU has efficacy similar to that of HIA FUDR given alone, but when closely monitored and adjusted appropriately, is not associated with toxic effects requiring treatment termination.

Chemoembolization for hepatocellular carcinoma.

Fifty-one patients with unresectable hepatocellular carcinoma (HCC) were treated with Gelfoam (absorbable gelatin sterile powder; The Upjohn Co, Kalamazoo, MI) chemoembolization. A mixture of Gelfoam powder, contrast media, and three drugs (doxorubicin, mitomycin, and cisplatin) was injected under fluoroscopic guidance via a percutaneous catheter into the hepatic artery until stagnation of blood flow was achieved. Of the 51 patients, 50 are assessable for response, and all are assessable for toxicity and complications. The median percent of liver replacement was 50% (range, 15% to 95%). By conventional response criteria, there were 12 partial responses (PRs) (24%), 13 minor responses (MRs) (26%), 12 stabilization of disease (SD) (24%), and 13 (26%) progressive disease (PD). Tumor liquefaction was noted on computed tomographic (CT) scan in 35 of 50 patients (70%). Of the 34 patients with elevated alpha-fetoprotein (AFP), 23 (68%) had a greater than 50% reduction following treatment. Responding patients were re-treated at the time of tumor progression if they still met the entry criteria. The median survival of assessable patients from the time of treatment was 207 days and from the diagnosis of the primary was 302 days. Fourteen patients remain alive at 3 months to 3 years following treatment. The vast majority of patients had transient pain, fever, nausea, and elevation in liver enzymes. Ascites developed in 14 patients. There were two treatment-related deaths: one from tumor hemorrhage and one from liver failure. Chemoembolization appears to have significant activity in patients with hepatocellular carcinoma and is relatively well tolerated.

Randomized crossover comparison of high-dose intravenous metoclopramide versus a five-drug antiemetic regimen.

In a randomized open crossover study, the antiemetic efficacy of a five-drug antiemetic regimen consisting of metoclopramide, dexamethasone, diazepam, diphenhydramine, and thiethylperazine was compared to that of high-dose metoclopramide. Thirteen patients treated with cisplatin combination chemotherapy regimens were evaluated. The study was terminated prior to accrual of the planned number of patients because of the statistically significant difference in efficacy between treatments found at interim analysis. The duration of nausea and number of vomiting episodes on the day of chemotherapy were significantly less (p less than 0.01) after receiving the five-drug combination. After receiving the five-drug regimen, 77% of the patients did not experience any episodes of vomiting on day 1, and 8% of patients had only one episode. In contrast, only 31% of patients treated with high-dose metoclopramide did not have any episodes of vomiting on day 1, and 61% of the patients had five or more episodes. None of the patients treated with the five-drug regimen required additional antiemetic administration. Although both regimens were, in general, well tolerated, when given the choice of continuing antiemetic therapies, 92% of the patients preferred the five-drug antiemetic combination.

Cancer chemotherapy in the elderly patient.

The elderly oncology patient has unique needs that require consideration in all aspects of care, from drug administration to nursing management. Aging is a highly individualized process and may present as a variety of clinical manifestations. As these age-related changes occur the oncology nurse must be prepared to recognize their potential impact on cancer treatment for each individual patient. To intervene successfully requires the knowledge and application of both geriatric and oncology nursing principles.