Non-surgical treatment for liver metastases.

The liver is a common site for developing metastatic disease. Although any malignancy can spread to the liver, the direct passage of blood from the gastrointestinal tract to the liver via the portal circulation results in a high rate of liver metastasis from gastrointestinal tract tumours. Various radiographical tests including computed tomography and magnetic resonance imaging can detect the majority of liver metastases. Surgical resection if feasible is the treatment of choice since it produces a 5-year survival rate of about 30%. However, the majority of the patients relapse after hepatic resection, 50% relapsing in the liver. Systemic chemotherapy produces response rates of 15-30% with a median survival of 10-12 months. It is estimated that 30,000 patients each year in the USA are candidates for regional hepatic therapy. Hepatic arterial chemotherapy, hepatic artery embolization, chemoembolization, cryosurgery, ethanol injection of the tumour and radiation therapy are being investigated as potential treatment options for such patients.

Phase II trial of postoperative adjuvant intraperitoneal cisplatin and fluorouracil and systemic fluorouracil chemotherapy in patients with resected gastric cancer.

PURPOSE: This study was performed to assess the short- and long-term toxicities and the impact on relapse pattern and survival of postoperative intraperitoneal (IP) cisplatin and fluorouracil (FU) plus systemic intravenous (IV) FU as adjuvant therapy for gastric cancer patients who are at high risk for recurrence after potentially curative resection (T2N1-2M0 or T3-4N(any)M0). PATIENTS AND METHODS: Starting 14 to 28 days after potentially curative resection of primary gastric cancers, 35 patients were given IP cisplatin 25 mg/m2 and FU 750 mg daily for 4 days; FU 750 mg/m2 was concurrently given as a continuous 24-hour i.v. infusion. Five cycles of therapy delivered at 1-month intervals were used. RESULTS: After a median follow-up of 24 months, 51% of patients remain alive and free of disease. Sixteen patients have recurred; 13 of 16 had an intraabdominal component, whereas three had extraabdominal failure only. Two major treatment-related toxicities were noted: neutropenia and a late toxicity of peritoneal fibrosis (sclerosing encapsulating peritonitis [SEP]). There was one postoperative death. Eleven patients underwent second laparotomy: five patients had SEP, two patients had bowel obstruction from adhesions unrelated to SEP, and four patients had recurrent cancer. Potential causes of SEP included an alkaline pH of infused FU and cisplatin that possibly led to activation of cisplatin before infusion. CONCLUSION: IP cisplatin and FU and concurrent systemic FU is a tolerable adjuvant therapy in the postoperative setting for patients with resected gastric cancer. The recommended dosage schedule with this technique is cisplatin 25 mg/m2 and FU 750 mg total dose IP with FU 500 mg/m2 as a continuous 24-hour infusion daily for days 1 to 4. SEP as a late toxicity, which was observed in 15% of patients, is treatable by surgical lysis of adhesions.

Cutaneous T-cell lymphoma presenting with diffuse lymphomatous infiltration of the peripheral nerves: response to combination chemotherapy.

A patient with nonepidermotropic cutaneous T-cell lymphoma presented with severe diffuse peripheral neuropathy that was the result of lymphomatous infiltration of the peripheral nervous system. There was no other evidence of systemic disease. The diagnosis was delayed because of the unusual presentation. A peripheral nerve biopsy was instrumental in establishing the etiology of the neuropathy. The patient achieved complete clinical remission with combination chemotherapy.

FAMTX versus etoposide, doxorubicin, and cisplatin: a random assignment trial in gastric cancer.

PURPOSE: The chemotherapy regimens of high-dose methotrexate, high-dose fluorouracil (FU), Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and leucovorin (FAMTX) and etoposide, Adriamycin, and cisplatin (EAP) have both been reported in nonrandom assignment trials to have high overall response rates and substantial complete response rates in patients with gastric cancer, as well as major toxicities of myelosuppression. Here we report a prospective, stratified, random-assignment comparison of the two combinations in previously untreated patients with advanced gastric cancer. PATIENTS AND METHODS: Sixty patients were entered onto the trial, 30 receiving EAP and 30 FAMTX. All patients had measurable or assessable tumor masses. Patient entry was stopped at the point when significant toxicity differences were seen at interim analysis. RESULTS: Response rates were similar between the two arms (FAMTX, 33% [95% confidence interval (CI), 16% to 50%]; EAP, 20% [95% Cl, 6% to 34%]). Three FAMTX and no EAP patients had complete remissions. The median survival for the two arms were similar (EAP, 6.1 months; FAMTX, 7.3 months). At 1 year, 7% of EAP and 17% of FAMTX patients were alive. EAP caused significantly more myelosuppression (leukopenia, P = .002; anemia, P = .03; thrombocytopenia, P = .0001) than did FAMTX. EAP also resulted in significantly longer hospitalizations per study month (8 v 5 days). Four EAP patients died of lethal toxicity, whereas no FAMTX patients died of treatment-related causes (P = .04). CONCLUSIONS: FAMTX is at least as active as EAP and is significantly less toxic. Although both regimens remain investigational, the toxicities of FAMTX are more manageable. Further studies involving FAMTX in both the adjuvant and advanced disease setting are underway.

Treatment of unresectable primary liver cancer with intrahepatic fluorodeoxyuridine and mitomycin C through an implantable pump.

Ten patients with unresectable primary liver cancer, eight of whom had elevated serum alpha-fetoprotein levels, were treated with intrahepatic fluorodeoxyuridine (FUDR) and mitomycin C administered through an implantable pump. Four patients had a partial response, and two had a minor response. The median survival from initiation of treatment was 14.5 months (range, 2 to 32 months), with patients receiving therapy for a median of 11.2 months. In general, the therapy was well tolerated; only one patient had treatment-related biliary sclerosis. In conclusion, the combination of intrahepatic FUDR and mitomycin C was an effective palliative regimen for unresectable primary liver cancer, even in the presence of elevated serum alpha-fetoprotein levels. Further studies are needed to confirm these findings and compare this regimen with other methods of treatment for hepatocellular carcinoma.

Therapy of upper gastrointestinal tract cancers.

Esophageal and gastric cancers are highly virulent tumors with an especially poor prognosis. They are rather common tumors in the United States with an anticipated annual incidence of approximately 32,000 new patients in 1991. Adenocarcinomas of the proximal stomach and lower esophagus are rapidly increasing in incidence; the reasons for this remain unclear. Endoscopic ultrasonography has offered a new dimension to staging especially of the primary tumor but also shows promise for more accurate identification of nodal metastasis. While stage remains the single most important prognostic variable, biological studies investigating tumor markers are a high priority; aneuploidy and HER-2/neu amplification or overexpression may predict poor outcome in gastric cancer. Esophageal and gastric cancers have a high local and distant failure rate when treated with conventional therapy. New developments in chemotherapy in the neoadjuvant and postoperative setting are under intense investigation in an attempt to improve prognosis for these diseases.