Faculty Bibliography

Treatment of colorectal cancer beyond surgical resection has had only minimal success in the past. Studies are therefore examining the most advantageous use of currently available treatment methods. Most experience with colorectal cancer has involved 5-fluorouracil; alternatives for adjuvant therapy include combination therapy, immunotherapy, and locoregional therapy. Some success has also been reported with portal vein infusion or intraperitoneal administration of chemotherapeutic agents. Comparison of recurrence data indicates that approximately one third of patients with extrapelvic colorectal cancer can be expected to have peritoneal seeding. Many factors, including selection of patients and chemotherapeutic agents, method of administration, devices used, and techniques for monitoring patients affect the results of any clinical study. Future directions for the adjuvant treatment of colorectal cancer might involve the addition of other agents to the intraperitoneal regimen or of whole abdominal or liver radiation, and also concomitant systemic or portal vein 5-fluorouracil.

The treatment of testicular cancer has undergone considerable evolution since the introduction of cisplatin and the widespread recognition of its curative potential in all stages of disease. Chemotherapy developments that have taken place include substitution of etoposide for vinblastine in some primary combinations and high-dose cisplatin regimens for patients with otherwise poor prognosis. Definition of timed survival restaging and reassessment of the role of radiation has taken place. In early disease stages, dissection of retroperitoneal nodes combined with either a short course of adjuvant chemotherapy or careful monitoring followed by salvage chemotherapy has yielded impressive results (greater than 90% cures) in node positive patients. These results have encouraged trials including careful follow up for patients with negative retroperitoneal and other findings (markers, computerized tomography) on clinical staging alone. Evolution of these treatment strategies should take place within the context of prospectively designed studies. In this brief overview of developments, we point out how the legacy from the successful application of chemotherapy will form the basis for additional achievements which will include the introduction of second-generation drugs and optimization of combined modality strategies.

In order to test the possible cardiac-sparing effect of doxorubicin administered by six-hour intravenous infusion and to prospectively evaluate the role of resting left ventricular ejection fraction in monitoring these patients, 33 women with advanced breast cancer were treated with combination chemotherapy containing 5-fluorouracil, cyclophosphamide, and doxorubicin. Doxorubicin was administered via a femoral catheter as a six-hour infusion. Cardiac function was monitored prior to therapy and at intervals during therapy by history and physical examination and by measurement of resting left ventricular ejection fraction with gated pool radionuclide angiography. Twenty-six responses were observed (complete response, seven [21 percent]; partial response, 19 [57 percent]). Systemic toxicity included alopecia, myelosuppression, and nausea and vomiting. There was a progressive fall in resting left ventricular ejection fraction during treatment from a median baseline value of 0.63. Mean fall from baseline left ventricular ejection fraction at a cumulative doxorubicin dose of 200 to 300 mg/m2 was 0.06 (p less than 0.005); at 301 to 449 mg/m2 it was 0.09 (p less than 0.0005); and at 450 mg/m2 or greater it was 0.15 (p less than 0.0005). Clinical congestive heart failure developed in three patients. Even though the decrease in left ventricular ejection fraction was often within the 'normal range' (left ventricular ejection fraction 0.50 or greater), these changes were progressive and appeared to be part of a continuum of doxorubicin-induced myocardial damage. Steady-state infusion levels of doxorubicin in plasma ranged from 90 to 120 nM. They confirm the hypothesis that lower concentrations can be achieved by continuous infusion rather than by bolus infusion. In this study, however, administration of doxorubicin by six-hour infusion did not appear to have a major cardiac-sparing effect. Studies of anthracycline cardiac toxicity should include determination of baseline left ventricular ejection fraction and serial observations during therapy. Failure to include deteriorations in function above an arbitrary cutoff point or to make observations only at higher cumulative doses may underestimate drug-induced myocardial damage

Twenty-one patients with advanced malignant melanoma were treated with dacarbazine at a dose of 800 mg/m2 as a single infusion and dactinomycin at a dose of 1.2 mg/m2 every 3 weeks. Hematologic toxicity was mild and gastrointestinal toxicity was tolerable. The response rate for evaluable patients was 22%, which included both men and women with visceral disease. Three of the four responses were complete. Durations of response were 4, 6, 9, and 48+ months. We conclude that dacarbazine can be safely and effectively given as a single dose along with dactinomycin. The possibility that this combination may be more effective than single agents in obtaining complete responses in patients with visceral disease must be explored further