Combination of Bolus 5-Fluorouracil, Folinic Acid and Mitomycin C in Advanced Gastric Cancer: Results of a Phase II Trial.

BACKGROUND: Gastric carcinoma still is a worldwide major cause of cancer death. Although various chemotherapy schedules yielded high response rates, median survival rarely exceeds 8-10 months. Many regimens are inevitably associated with significant toxicity which jeopardizes their value as palliative treatment, especially in patients with reduced performances status. Therefore, we initiated a phase II study for the treatment of advanced gastric carcinoma using a bolus regimen with mitomycin C (MMC), 5-fluorouracil (5-FU) and folinic acid (FA), allowing the enrollment of elderly patients or those with reduced performance status (WHO grade 2). PATIENTS AND METHODS: Between 1996 and 1998 we recruited a total of 58 patients with advanced gastric cancer to receive bolus MMC 3 mg/m(2), 5-FU 450 mg/m(2), and FA 100 mg/m(2) on days 1-3. Treatment was repeated on day 22. 53 patients met the inclusion criteria: male n = 36, female n =17; median age 65 (range 26-81); mean WHO status 1 (range 0-2). RESULTS: Out of 53 patients 50 were evaluable for response, all 58 patients who received therapy were evaluable for toxicity. Eleven patients (22%) achieved partial remission (95% CI: 11.5 -36.0%), 24 (48%) no change and 15 (30%) were progressive. Median overall survival was 11.5 months, the median time to progression 6.0 months. Out of 290 treatment cycles the worst toxicities observed (WHO 2/3/4) were as follows: anemia 13/3/1, leukopenia 19/1/1, thrombopenia 11/3/0, nausea/emesis 11/2/0, infections 2/1/0, diarrhea 14/2/0, and stomatitis 6/1/1. One patient developed hemolytic-uremic syndrome. CONCLUSIONS: The tumor control rate (PR + NC) of 70% was comparable to established chemotherapy regimens, while median overall survival was promising. Toxicity was mild, allowing the treatment especially for elderly patients and on outpatient basis. Copyright 2000 S. Karger GmbH, Freiburg

Adjuvant therapy with edrecolomab versus observation in stage II colon cancer: a multicenter randomized phase III study.

BACKGROUND: In a phase III study recruiting patients with stage II colon cancer the effect of adjuvant therapy with edrecolomab, a murine monoclonal antibody to the cell-surface glycoprotein 17-1A, was compared to observation alone. PATIENTS AND METHODS: From January 1997 until July 2000 a total of 377 patients were postoperatively stratified according to tumor stage (T3 vs. T4) and center, and randomly allocated to either treatment with edrecolomab (cohort A, n = 183) or observation (cohort B, n = 194). Patients in cohort A received a total of 900 mg edrecolomab. The study was terminated prematurely because of discontinuation of drug supply in Germany. RESULTS: 305 patients were eligible for the primary endpoint of overall survival and 282 patients for disease-free survival. After a median follow-up of 42 months overall survival and disease-free survival were not significantly different. Toxicity was mild. CONCLUSIONS: In the present study, postoperative adjuvant treatment with edrecolomab in patients with resected stage II colon cancer did not improve overall or disease-free survival.

[HLA-B27-negative sacroiliitis as a complication of inflammatory forms of acne: case reports and review of the literature]. / HLA-B27-negative Sacroiliitis als Komplikation entzündlicher Akneformen: Fallberichte und Literaturübersicht.

In this review, three patients with severe inflammatory acne accompanied by a distinct rheumatologic syndrome are discussed together with 44 similar cases reported in the literature. This syndrome, here referred to as "acne-associated arthritis (AAA)" usually involves male teenagers and twins. The most characteristic clinical findings relate to the axial skeleton as well as the sterno-costo-clavicular region. Although no association with HLA-B27 has been found, AAA shares a number of clinical, radiological and histomorphological features with seronegative spondylarthropathies. Furthermore, nosological connections seem to exist with a number of ill-defined "hyperostotic osteoarthropathies." Similar characteristics are known from other "pustulotic or neutrophilic dermatosis." The hypothesis of an infectious etiology of AAA has not been substantiated. Responses to systemic antibiotics are generally disappointing, whereas steroids have been shown to exhibit some therapeutic efficacy.

Adjuvant radio-chemotherapy in stage II-III rectal cancer with 24-hour infusion of high-dose 5-fluorouracil and folinic acid: evaluation of feasibility.

BACKGROUND: Postoperative radio-chemotherapy has been established as standard treatment for stage II and III rectal cancer patients in the last decade. To improve the efficacy of this therapy, we decided to evaluate continuous 24-hour infusion of 5-fluorouracil (5-FU) with folinic acid (FA) in combination with local radiation versus standard bolus 5-FU/FA with local radiation in a randomized study. Here we report on the first 28 patients to receive the experimental treatment. PATIENTS AND METHODS: Patients with stage II and III rectal cancer received weekly 2-hour infusions of FA 500 mg/m2 followed by continuous 24-hour infusions of 5-FU 2,600 mg/m2 postoperatively via a Port-A-Cath system. The first cycle included 8 consecutive weekly administrations, the 1st-4th in full dose, the 5th-8th with 50% reduced dose while local irradiation (45 or 50.4 Gy) was performed. Thereafter, two further chemotherapy cycles (6 weekly administrations, 100% dose) followed. RESULTS: 28 patients received continuous 5-FU/FA treatment, of whom only 21 were evaluable for tolerability. 19 patients (90.4%) completed the first cycle, only 14 patients entered the second treatment cycle. Especially during the combined radiochemotherapy, increased toxicity was observed with grade III/IV diarrhea (n = 2), nausea (n = 1), leukopenia (n = 1), and cardiac toxicity (n = 1). CONCLUSION: The high rate of premature treatment dropout indicate that the chosen schedule of weekly high-dose 5-FU/FA continuous infusion and combined postoperative radiotherapy should not be recommended for further use in postoperative adjuvant treatment.

Adjuvant chemotherapy in stage III colon cancer with 5-fluorouracil and levamisole versus 5-fluorouracil and leucovorin.

BACKGROUND: Adjuvant chemotherapy for colon cancer has been established during the past decade. From 1990 until recently treatment with 5- fluorouracil (5-FU) and levamisole (LEV) lasting 12 months was recommended as standard treatment. At the initiation of this study in 1993 improvement of adjuvant therapy was expected by the modulation of 5-FU with folinic acid (FA). Therefore, we decided to perform a prospective randomized multicenter trial to compare standard 5-FU/LEV to 5-FU/FA for either 6 or 12 months. PATIENTS AND METHODS: Patients with stage III colon cancer after curative en bloc resection were randomized in 3 treatment groups: arm A (5-FU/LEV, weekly, 12 months), arm B (5-FU/FA, days 1-5, every 4 weeks, 12 months) and arm C (like B, 6 months). RESULTS: Between March 1993 and November 1997, 180 patients were randomized into the study, 155 were eligible for further evaluation. The interim analysis in November 2000 showed no significant difference for recurrence and disease-free survival in arm B and C, therefore the data from both 5-FU/FA treatment arms (B+C) were combined for comparison with 5-FU/LEV-treatment (A). Most pronounced toxicity in all treatment arms was mild nausea, loss of appetite and leukopenia. A tendency for more diarrhea and stomatitis was observed in arm B+C. After a median follow-up of 36.2 months no significant difference was seen for disease free survival (p = 0.9) and overall survival (p = 1.0). 3-year recurrence rates were 39.6% in arm A and 39.1% in arm B+C, 3-year survival rates amounted to 74.1% in arm A and 74.9% in arm B+C. CONCLUSION: Only a limited number of patients could be recruited in this study. The observed data support the results of other studies, which concluded that 6 months (or 12 months) treatment with 5-FU/FA is equivalent to 12 months treatment with 5-FU/LEV. Therefore the 6 months treatment with 5-FU/FA can be supported as standard for adjuvant therapy of stage III colon cancer.