PURPOSEMore than 50,000 patients in the United States will present each year with liver metastases from colorectal cancers. The current study was performed to determine if liver resection for colorectal metastases is safe and effective and to evaluate predictors of outcome.MATERIALS AND METHODSData for 456 consecutive resections performed between July 1985 and December 1991 in a tertiary referral center were analyzed.RESULTSThe perioperative mortality rate was 2.8%, with a mortality rate of 4.6% for resections that involved a lobectomy or more. The median hospital stay was 12 days and only 9% of patients were admitted to the intensive care unit. The 5-year survival rate is 38%, with a median survival duration of 46 months. By univariate analysis, nodal status of the primary lesion, short disease-free interval before detection of liver metastases, carcinoembryonic antigen (CEA) level greater than 200 ng/mL, multiple liver tumors, extrahepatic disease, large tumors, or positive resection margin was predicti...

Liver resection for colorectal metastases.

The clinical pharmacology and use of antimicrotubule agents in cancer chemotherapeutics.

The earliest reports on the therapeutic use of metals or metal-containing compounds in cancer and leukemia date from the sixteenth and nineteenth centuries. They were forgotten until the 1960s, when the anti-tumour activity of the inorganic complex cis-diammine-dichloroplatinum(II) (cisplatin) was discovered. This led to the development of other types of non-organic cytostatic drugs. Cisplatin has developed into one of the most frequently used and most effective cytostatic drugs for the treatment of solid carcinomas. Numerous other metal compounds containing platinum, other platinum metals, and even non-platinum metals were then shown to be effective against tumours in man and experimental tumours in animals. These compounds comprise main-group metallic compounds of gallium, germanium, tin, and bismuth, early-transition metal complexes of titanium, vanadium, niobium, molybdenum, and rhenium, and late-transition metal complexes of ruthenium, rhodium, iridium, platinum, copper, and gold. Several platnium complexes and four non-platnium-metal antitumour agents have so far entered early clinical trials. Gallium trinitrate and spirogermanium have already passed phase II clinical studies and have shown limited cytostatic activity against certain human carcinomas and lymphomas. The two early-transition metal complexes budotitane and titanocene dichloride have just reached the end of phase I clinical trials and have been found to have an unusual pattern of organ toxicity in man. Titanocene dichloride will soon enter phase II clinical studies.

Complexes of metals other than platinum as antitumour agents.

This review summarizes data demonstrating the safety and efficacy of liver resection for colorectal metastases. Hepatic resection in appropriately selected patients remains the only potentially curative treatment for patients with such metastases. Recommendations for preoperative patient evaluation, patient selection, adjuvant therapy, and postoperative follow-up are presented. Other surgical modalities utilized in the treatment of unresectable or recurrent hepatic colorectal metastases, including ablative modalities and surgical delivery of regional chemotherapy, are described.

Surgical therapy of hepatic colorectal metastasis.

4′-epi-doxorubicin, a new analogue of doxorubicin: a preliminary overview of preclinical and clinical data

Tamoxifen (NSC-180973; ICI-46474) can provide palliation to patients with advanced breast cancer whose tumors contain estrogen-binding proteins (EBP). The drug is most effective in patients with bone metastasis and minimal prior therapy. In the present study, 72 patients with advanced breast cancer were evaluated for their response to oral tamoxifen therapy administered at a dose of 20 mg twice daily. Twenty-eight of 72 patients (38%) demonstrated objective responses to tamoxifen therapy. For patients with a positive EBP and no prior chemotherapy, eight of 11 (74%) responded. No patient possessing a tumor negative for EBP achieved a remission. Patients with tumors that possessed normal arylsulfatase B and glucose-6-phosphate dehydrogenase enzyme activities responded most favorably to tamoxifen therapy. These results demonstrate that tamoxifen is effective in the treatment of patients with advanced breast cancer, and EBP and specific enzymes might be useful in selecting the patients for hormone manipulation.

Therapeutic use of tamoxifen in advanced breast cancer: correlation with biochemical parameters

Spirogermanium is a new azaspirane antitumor agent, with the metal germanium substituted for a one-carbon moiety in the ring structure This drug inhibits DNA and RNA synthesis in HeLa cells, is cytotoxic in vitro, and has curative in vivo antitumor activity against the ascitic Walker 256 carcinosarcoma in rats No hematologic toxicity was recorded during the preclinical toxicologic evaluation The principal clinical toxic effects observed in this phase I trial were neurologic, manifested as lethargy, dizziness, and ataxia, while a grand mal seizure was produced after an accidental overdose There was no evidence of hematologic, renal, or hepatic toxicity A partial response was achieved in a patient with a well-differentiated lymphocytic lymphoma We recommend that phase II trials be conducted with a twice or thrice weekly dose of 50-80 mg/m2, administered in a 30-minute iv infusion

Phase I clinical trial of spirogermanium.

We report a phase II trial of 5-fluorouracil (5-FU), methyl-CCNU, and vincristine (FMV) combination chemotherapy in advanced colorectal carcinoma. Ten of 25 patients (40%) achieved an objective tumor regression after treatment with FMV chemotherapy. The main toxicities of FMV were hematologic and gastrointestinal. 5-FU was administered in a weekly rather than a loading-dose schedule which allowed for sensitive adjustment of drug dosages according to hematologic toxicity; only 16% of the patients (four of 25) had a wbc count less than 2000 cells/mm3. FMV is significantly more active than 5-FU alone in the treatment of advanced colorectal cancer; however this regimen does not significantly improve survival in responding patients.

5-Fluorouracil (5-FU), methyl-CCNU, and vincristine in the treatment of advanced colorectal cancer: phase II study utilizing weekly 5-FU.

An in vitro assay system to measure the production of phosphorylated nucleotide products of 5-FU by human tumor cytosols is described. Samples from 11 patients with breast cancer treated with 5-FU-containing chemotherapy regimens were assayed. Significant differences were seen in quantitative and qualitative patterns of phosphorylation between samples from chemotherapy responding and nonresponding patients. Both the rate of 5-fluorodeoxyuridylate production and the amount of fluorinated nucleotide triphosphate produced were significantly increased (P less than 0.05) in patients responding to chemotherapy. The latter finding may be attributed to the demonstration of significantly higher nucleoside diphosphate kinase levels in the tumors of responding patients. Further study of this in vitro assay system as a potential system for prospectively predicting clinical response to fluorinated pyrimidines is indicated.

The potential for clinical application of in vitro assays predicting 5-FU sensitivity in man.

CAMP (cyclophosphamide, doxorubicin, methotrexate, and procarbazine) for epidermoid and large cell anaplastic carcinoma of the lung.

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