Search

Previous research has indicated that the slow, continuous infusion of 5-fluorouracil in the treatment of advanced colorectal cancer is more effective in producing responses than is the administration of the drug in single boluses. While a response rate of 30 percent was observed among the patients given protracted infusional 5-fluorouracil (PIF) and only a seven percent response rate observed among the patients receiving bolus injections, the advantage in response rate did not produce a statistically significant improvement in survival. While the PIF patients achieved greater survival at 18 and 24 months, the difference did not achieve statistical significance. In order to fine-tune the chemotherapeutic treatment of advanced colorectal cancer, the researchers have now evaluated the effects of adding a weekly bolus of cisplatin to the continuous infusion of 5-fluorouracil. A total of 184 patients with advanced metastatic colorectal cancer, never treated before with chemotherapy, were given the protracted infusion of 5-fluorouracil at 300 milligrams per meter squared of body area per day for 10 weeks. The patients were randomly assigned to receive or not receive cisplatin in addition to this treatment; each week, some patients also received a bolus of 20 milligrams per meter squared cisplatin. Of the patients who were fully evaluable for response and survival, 85 received both drugs while 83 received 5-fluorouracil alone. The results were almost identical for the two groups. Thirty-five percent of the patients in the 5-fluorouracil-only arm responded to treatment; 33 percent of those receiving both drugs responded. Likewise, the median survival of the patients receiving 5-fluorouracil was 11.8 months; for the patients receiving 5-fluorouracil and cisplatin, the median survival was 11.3 months. The results indicate that the addition of cisplatin to the chemotherapeutic regimen provides no benefit to the patients. The authors suggest that research efforts might be better spent determining dosage schedules of 5-fluorouracil which provide maximum effect. (Consumer Summary produced by Reliance Medical Information, Inc.)

In patients treated nonsurgically for “limited” small cell carcinoma of the lung, the most frequent site of relapse is within the chest We have treated patients with clinical Stage III M0 disease (T3 and/or N2, M0) by two cycles of chemotherapy, surgical resection of the primary site and mediastinal nodes, and continued chemotherapy thereafter. Since May, 1979, the regimen has consisted of cyclophosphamide, doxorubicin, vincristine, and etoposide on a 3 week cycle. The first 12 patients so treated had partial or complete remission after two cycles. Resection was technically not possible in two. Residual small cell carcinoma was not identifiable in the specimens from two of the 10 patients undergoing resection. Microscopic tumor extended to a resection line in two of the eight with residual tumor. Malignant tissue appearing to have the structure of papillary adenocarcinoma was found in hilar and paratracheal nodes in one patient, but nowhere in the resected lung; some residual small cell carcinoma remained in the lung. Nuclear ballooning and eosinophilic inclusions were noted in cells still identifiable as small cell carcinoma in one case. Marked fibrotic scarring was noted in eight cases, acute and organizing bronchopneumonia in three, and multiple small parenchymal abscesses in one case. Long disease-free survival occurred in one patient, in whom residual tumor could not be found in the specimen; in at least one more in whom residual tumor was present; and even in one patient in whom tumor was present at the bronchial resection line.

Surgical resection offers distinct theoretical advantages as the “local” modality in treatment of Stage I and II small cell carcinoma of the lung. We have treated 10 such patients by initial resection since 1975; all survivors but one received adjuvant chemotherapy for the full course thereafter. One patient died of a pulmonary embolus; the other nine remain without evidence of disease from 7 to 69 months after resection. A trial was undertaken of extended indications for resection in selected patients with Stage III-MO*** disease. Criteria for patient selection have been developed gradually; these exclude patients for reasons of refusal, physiological inadequacy, disease unsuited to gross total eradication, or lack of adequate initial response to chemotherapy. Of six patients who survived the exclusion criteria and underwent resection, one has had a relapse at 26 months. All others remain without evidence of disease, 5 to 25 months after the start of treatment. We believe that systematic patient selection on the basis of defined criteria will identify a subset of patients having markedly improved chances for disease control. This group may represent as many as half of the patients first presenting with localized or MO disease. Patients excluded as candidates for resection have continued to receive standard nonsurgical combined-modality therapy.

We reviewed survival of patients with clinically localized small cell carcinoma of the lung treated by surgical resection, combination chemotherapy, and prophylactic cranial irradiation. Long-term survival was defined as continuing complete remission 30 months after the start of treatment. Initial TNM staging determined the course of treatment. Ten patients with disease in Stages I and II were treated over 30 months ago by initial resection followed by the full course of chemotherapy. Only one has had a relapse, whereas 80% remained disease-free at 30 months. Five of these patients have passed 5 years. Four patients with T3 N1 disease were treated by two cycles of chemotherapy, surgical resection, and cranial irradiation plus resumption of chemotherapy thereafter; two remained in remission at 30 months. Sixteen patients initially with N2 disease were treated according to the same schedule; 10 of the 16 underwent successful resection. All 16 patients have had a relapse, but the relapse occurred very late in three—at 27, 30, and 37 months. The reasons for the apparently poor prognosis of N2 disease are not clear. Considerations of tumor response kinetics and somatic mutation suggest that these biologic factors are fundamentally responsible. Other studies may find disease control achieved in a very few patients with N2 disease.