New Approaches to Adjuvant Therapy of Colorectal Carcinoma Including Current German Activities

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Background: Adjuvant chemo- and radiotherapy for colorectal carcinoma has been established during recent years. Currently treatment with 5-fluorouracil (5-FU) and levamisole (LEV) is recommended as standard treatment for Dukes C colon cancer; for rectal cancer (Dukes B2-C) radiation and 5-FU single-agent chemotherapy is considered treatment of choice. Progress for therapy is expected by the introduction of folinic acid (FA) and 5-FU as chemotherapy. However, there has been concern about increased toxicity; therefore the object of this report is to present toxicity data from two ongoing adjuvant treatment trials on colorectal cancer. Method: In the study for colon cancer (Dukes C), 3 treatment groups were compared: arm A (5-FU/LEV, weekly, 12 months), arm B (5-FU/FA, days 1-5, every 4 weeks, 12 cycles) and arm C (like B, 6 cycles). In the rectal cancer study (Dukes B2-C) arm A (5-FU/FA, days 1-5, every 4 weeks, 12 cycles) and arm B (like A, 6 cycles) were compared. During the second cycle radiation up to 50.4 Gy was performed and chemotherapy was applied weekly. Results: From 1993 until December, 1994 a total of 146 patients were recruited in both studies. Data from 92 completely documented patients, who received adjuvant treatment either with 5-FU + FA (n = 76) or 5-FU + LEV (n = 16), could be analysed for toxicity patterns. In the group with 5-FU + LEV one case with WHO grade-IV toxicity (hae-matological, gastrointestinal) and 6 events with grade-III toxicity occurred (CNS, alopecia, fever). In the 5-FU + FA group 15 events with grade-III toxicity were found, most of these gastrointestinal, and one case of cardio-toxicity. All patients recovered, and treatment-related death was not seen. Conclusion: For the majority of patients therapy was tolerable. Preliminary data of our two adjuvant trials in colon and rectum carcinoma using chemotherapy or radio-chemotherapy suggest that treatment with 5-FU + LEV and 5-FU + FA is safe but has to be performed under adequate control and dose adjustment.

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Adjuvant Chemotherapy with 5-Fluorouracil and Folinic Acid in Colorectal Cancer: Evaluation of Toxicity

Hartung¹,

Queißer²,

Diezler

et al. 1996

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“…Justification for this decision could also be found in other studies currently being under taken in Germany, in which patients undergo an adjuvant therapy following curative resection of a colorectal carci noma. As stated in a review article [2], none of these studies include a control group. -T h e median follow-up time in the studies were dissimilar (15 months in comparison to 3 years) due to the neurotoxic side effects which, as already mentioned, led to the discon tinuation of the Stuttgart study.…”

Section: Discussionmentioning

confidence: 99%

Levamisole and 5 Fluorouracil as an Adjuvant Therapy for Patients after Curative Resection of Colon Carcinoma Dukes’ Stage C (TNM III): More Disadvantages than Advantages

Wassner¹,

Heidemann²

1996

Background: An American National Intergroup has shown that the risk of cancer recurrence could be reduced by 41% in a group of patients who had undergone a curative resection of colon carcinoma Dukes’ stage C (regional nodal involvement) if they were subsequently treated with levamisole and 5-Fluorouracil (5-FU) in comparison to a group of patients who had undergone surgery only. The mortality rate was reduced by 33%. The study carried out by the Oncological Center of Stuttgart aimed to reproduce these results. Patients and Methods: Having had a curative resection of a colon carcinoma stage TNM III (Dukes’ C), 62 patients were then treated with levamisole and 5-FU for 1 year. Inclusion criteria and levels of dosage of levamisole and 5-FU were the same as those in the study carried out by the National Intergroup. Due to the extremely positive results shown in the National Intergroup study it was considered unethical to include in the Stuttgart study a control group of patients who had undergone surgery only. Results: As severe side effects were observed in the study of the Oncological Center of Stuttgart, the study was already discontinued after a median follow-up time of 15 months (range 1 month to 3.5 years) and the patient data were evaluated. The prognostically relevant characteristics of the levamisole and the 5-FU patient groups in both studies were very nearly identical. This would allow a direct comparison between the two studies. 3.5 years after the beginning of the treatment, 63% of the levamisole and 5-FU patients in the Intergroup study had no cancer recurrence in comparison to 39% of patients in the Stuttgart study. This difference is statistically highly significant. Severe neurotoxic side effects were observed in patients in the Stuttgart study. 2 patients developed multifocal leucencephalopathy, 2 patients fell into coma. Conclusions: As the Stuttgart study could not include a control group of patients who had undergone surgery only, the study is not able to proof the possible ineffectiveness of an adjuvant therapy with levamisole and 5-FU. Considering the study results, however, it would be a sensible and justifiable decision to include a control group in future randomized studies to examine the effectiveness of this adjuvant therapy. We recommend that those patients treated with levamisole and 5-FU should be watched very carefully for neurotoxic side effects

“…Cur rently several studies have been initiated to improve adjuvant treatment of colorectal tumors. Of special interest is the effec tiveness of 5-FU and folinic acid (FA) in the adjuvant setting [2]. For palliative first-line treatment of colorectal cancer the combination of 5-FU and FA is generally accepted [5].…”

Section: Introductionmentioning

confidence: 99%

Effective Secondary Neoadjuvant Chemotherapy with 5-Fluorouracil and Folinic Acid in a Patient with Cancer of the Colon

Hartung¹,

Jentschura²,

Trede³

et al. 1995

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Background: Adjuvant chemotherapy of high-risk carcinomas of the colon and rectum has recently been established. However, early chemotherapy is not yet proven to have a positive influence on the resectability and prognosis in patients with synchronous distant metastases. Case Report: We report on a 63-year-old patient who suffered from colon cancer with synchronous hepatic metastases. In August 1992, a left-sided hemicolectomy was performed for pT3, pN1, pM1 (hepar.) G2 cancer of the descending colon. Intraoperatively 2 hepatic metastases were found. Following a postoperative chemotherapy with 5-fluorouracil (5-FU) and folinic acid (FA) (3 cycles) a significant regression of the metastases became evident. In absence of further distant metastases and local recurrence the potentially curative resection of the hepatic metastases was performed successfully by segmentectomy of the segments 4 and 8 in December 1992. The postoperative course was uneventful. The histopathological examination showed complete necrotic and devitalized tumor tissue. For one more year, until September 1993, adjuvant chemotherapy with 5-FU and FA was performed. Until now (December 1994) the patient has remained tumor free. Conclusions: In carcinoma of the colon with synchronous distant metastases the combination of 5-FU and FA might serve as a potentially successful neoadjuvant chemotherapy regimen.