Judy L. Chase

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.

Surgery after downstaging of unresectable hepatic tumors with intra-arterial chemotherapy.

Background: This retrospective study was performed to assess the outcome among patients who underwent hepatic resection or tumor ablation after hepatic artery infusion (HAI) therapy downstaged previously unresectable hepatocellular carcinoma (HCC) or liver metastases from colorectal cancer (CRC).Methods: Between 1983 and 1998, 25 patients with HCC and 383 patients with hepatic CRC metastases were treated with HAI therapy for unresectable liver disease. We retrospectively reviewed the records of 26 (6%) of these patients who underwent subsequent surgical exploration for tumor resection or ablation.Results: At a median of 9 months (range 7–12 months) after HAI treatment, four patients (16%) with HCC underwent exploratory surgery; two underwent resection with negative margins, and the other two were given radiofrequency ablation (RFA) because of underlying cirrhosis. At a median postoperative follow-up of 16 months (range 6–48 months), all four patients were alive with no evidence of disease. At a median of 14.5 months (range 8–24 months) after HAI therapy, 22 patients with hepatic CRC metastases underwent exploratory surgery; 10 underwent resection, 6 underwent resection and RFA or cryotherapy, and 2 underwent RFA only. At a median follow-up of 17 months, 15 (83%) of the 18 patients with CRC who had received surgical treatment had developed recurrent disease; the other 3 died of other causes (1 of postoperative complications) within 7 months of the surgery. One patient in whom disease recurred underwent a second resection and was disease-free at 1 year follow-up.Conclusions: Hepatic resection or ablation after tumor downstaging with HAI therapy is a viable option for patients with unresectable HCC. However, given the high rate of recurrence of metastases from CRC, hepatic resection or ablation after downstaging with HAI should be used with caution.

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.

Modern systemic chemotherapy in surgically unresectable neoplasms of appendiceal origin: a single-institution experience.

Appendiceal neoplasms include tumors ranging from benign‐appearing cells with widespread mucin deposits to aggressive poorly differentiated signet ring cell adenocarcinomas. Traditionally, these tumors are treated with cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy. For some patients, cytoreductive surgery is not an option, and minimal published data exist in the management and outcome of these patients. A retrospective analysis was conducted to determine the benefit of modern systemic chemotherapy in patients with disseminated appendiceal neoplasm who were not considered optimal candidates for cytoreductive surgery.

Feasibility of adjuvant hepatic arterial infusion of chemotherapy after radiofrequency ablation with or without resection in patients with hepatic metastases from colorectal cancer

AbstractBackground: The safety of combined hepatic artery infusion chemotherapy (HAI) and radiofrequency ablation (RFA) for liver metastases has not been assessed. We conducted a study to determine the feasibility of using HAI after RFA for colorectal cancer (CRC) liver metastases. Methods: Between 1996 and 2001, patients with hepatic metastases from CRC were enrolled onto a prospective study of RFA plus HAI consisting of continuous-infusion floxuridine and bolus fluorouracil. Surgical complications, treatment-related toxicities, and patient outcomes were recorded. Results: Fifty patients were treated with RFA and HAI with or without resection. A median of two lesions per patient, with a median greatest diameter of 2.0 cm, were treated with RFA. Postoperative complications, including 1 death, occurred in 11 of 50 patients. Toxicity from HAI was relatively mild. At 20 months’ median follow-up, 32% of patients remained disease free. Ten percent of patients had recurrences at the site of RFA, 30% developed new liver metastases, and 48% developed extrahepatic disease. Conclusions:RFA of CRC liver metastases followed by HAI is feasible and is associated with acceptable complication and toxicity rates. The high rate of disease recurrence in our patients indicates that novel combinations of regional and systemic therapies are needed to improve patient outcomes.

Toxicity and Outcomes Associated with Surgical Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for Patients with Sarcomatosis

BackgroundTreatment of peritoneal recurrence following surgical resection of intra-abdominal sarcomas presents a significant challenge to clinicians. Historically, treatment with systemic chemotherapy has been ineffective and surgical resection alone has not been durable. We prospectively evaluated the feasibility of cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin (CDDP) alone or in combination with mitoxantrone (MITOX) for the treatment of sarcomatosis.MethodsTwo phase I trials of HIPEC were conducted (1998–2003). Eligible patients with evidence of sarcomatosis underwent cytoreductive surgery followed by HIPEC. In the first trial, CDDP dosing was established as 90 mg/m2 with a perfusate time of 90 minutes and temperature of 41°C. In the second trial, MITOX (20 mg/m2) was instilled following perfusion with CDDP. Toxicity, efficacy, and quality of life (QOL) were evaluated.ResultsA total of 28 patients were enrolled in the two trials. We noted a higher overall toxicity score and complication rate with combination CDDP/MITOX versus CDDP alone and shorter overall survival duration (5.5 months vs 16.9 months, respectively). In addition, local recurrence rates were similar in both groups (CDDP 79% vs CDDP/MITOX 68%). As expected, QOL scores at 6–8 weeks following HIPEC were 15–25% lower than the baseline scores; however, they returned to baseline at 3–6 months.ConclusionsAlthough the HIPEC technique is feasible for patients with sarcomatosis, it is associated with significant toxicity and limited clinical benefit. Combination CDDP/MITOX failed to demonstrate any benefit over CDDP alone; moreover, there was an increase in toxicity.

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.

Clinical Use of Anti-Vascular Endothelial Growth Factor Monoclonal Antibodies in Metastatic Colorectal Cancer

Vascular endothelial growth factor (VEGF) is the most potent proangiogenic factor and has been identified as an important target of cancer therapy Blocking endothelial cell VEGF activity inhibits tumor angiogenesis; normalizes tumor vasculature, facilitating improved chemotherapy delivery; and prevents the recruitment of progenitor cells from the bone marrow. Bevacizumab, the only United States Food and Drug Administration (FDA)‐approved anti‐VEGF agent, is a monoclonal antibody that inhibits the binding of VEGF to VEGF receptors. The addition of bevacizumab to standard first‐ and second‐line chemotherapy regimens for the treatment of metastatic colorectal cancer improves overall and progression‐free survival times and increases the time to disease progression. Studies are evaluating bevacizumab as adjuvant therapy. The optimal bevacizumab dosage is unknown, but 5 mg/kg every 2 weeks is currently recommended for initial therapy. A surrogate efficacy marker is needed to optimize bevacizumab use, both for dose and patient selection; the clinical applicability of several surrogate efficacy markers is being evaluated. Generally, bevacizumab is well tolerated; however, several serious adverse effects that may occur (e.g., hypertensive crisis) can usually be appropriately prevented or managed. Although current recommendations suggest the administration of the first bevacizumab dose over 90 minutes to prevent infusion‐related hypersensitivity reactions, recent study results show that 5 and 10 mg/kg can safely be administered over 10 and 20 minutes, respectively. Whether the addition of bevacizumab to metastatic colorectal cancer treatment regimens is a cost‐effective treatment option is unknown; health economic studies are needed. When used for FDA‐approved indications or for off‐label indications being evaluated in select clinical trials, Medicare reimburses for bevacizumab therapy.

Hepatic arterial infusion chemotherapy with complete hepatic venous isolation and extracorporeal chemofiltration: a feasibility study of a novel system.

When chemotherapeutic drugs with low liver extraction are used for hepatic arterial infusion (HAI), dosage limits are usually determined by systemic rather than hepatic toxicity. If such agents could be administered by HAI at dosages limited by hepatic toxicity, regional drug exposure and therapeutic efficacy might be significantly enhanced. We report herein a novel system that achieves complete hepatic venous isolation using a dual-balloon vena cava catheter that can be inserted percutaneously. This catheter is connected to a carbon fitter in an extracorporeal venous bypass circuit to recover drug that is not absorbed by the liver after HAI. The hemodynamic response to this system was evaluated in six pigs. When the anlmals were placed on the extracorporeal circuit, we observed a 22% decrease in cardiac output that was well tolerated without significant change in blood pressure. When the filter was incorporated into the clrcuit, cardiac output was significantly reduced (50%); however, continuous infusion of phenylephrine rapidly chemofitration ethicacy was pertormed in four of the six animals, the remaining two animals being used only to assess hemodynamic response. One each of the four tested animals received either doxorubicin (3 or 9 mg/kg), mltomycln C (1 mg/kg), or cisplatin (1 mg/kg) by HAI. The filler removed over 90% of hepatic venous doxorubicin and mitomycin C and 65% of hepatic venous clsplatin. This feasibility study confirms that hepatic venous isolation with chemofiltration can significantly reduce systemic exposure to high-dose chemotherapeutic agents given by HAI.

ASHP Guidelines on Preventing Medication Errors with Chemotherapy and Biotherapy

The purposes of these guidelines are to define best practices for the safe use of chemotherapy and biotherapy agents and to assist practitioners in improving their medication-use systems to prevent medication errors and patient harm from these agents. Although the guidelines are intended primarily