[Peripheral polyneuropathy and bilateral optic neuropathy during treatment of chronic hepatitis C]. / Periphere Polyneuropathie und beidseitige Optikusneuropathie unter Behandlung einer chronischen Hepatitis C.

HISTORY AND CLINICAL FINDINGS: A 54-year-old female patient with recently confirmed chronic hepatitis C, genotype Ib and positive HCV-RNA was admitted for interferon induction therapy. EXAMINATIONS: Physical examination findings were normal. Ultrasound examination of the abdomen revealed slightly compacted liver structure with otherwise no pathological findings. Laboratory results showed marginally increased GPT value at 46 U/l with HCV-RNA of 769,000 U/ml. All other laboratory results were within the reference range. There was no indication for autoantibodies. THERAPY AND COURSE: After one-week induction therapy with interferon-alpha (IFN-alpha2a) plus ribavirin and amantadine, maintenance therapy with pegylated interferon-alpha (PEG-IFN-alpha2a) plus ribavirin and amantadine was initiated. Complete virus elimination was achieved after two and a half months. Five months after onset of therapy, painful peripheral neuropathy of the limbs occured and after one more month, severe vision impairment with opticus neuropathy and bilateral papilledema developed. Simultaneously, peripheral polyneuropathy progressed with additional motoric deficits. Interferon therapy was terminated and the patient received high-dose corticosteroids which resulted in an improvement of neuropathic complaints. Eight months later, only discrete bilateral vision impairment with optic nerve atrophy remained. CONCLUSION: Side effects occurring with interferon-alpha therapy and pegylated interferon-alpha therapy are generally low and well tolerated. However, in individual cases - as in our patient - side effects including severe peripheral neuropathy and optic neuropathy have been observed. In these cases, interferon therapy must be terminated immediately as severe damage of nerves may result.

Successful treatment of steroid refractory active ulcerative colitis with natural interferon-beta--an open long-term trial.

INTRODUCTION: In some steroid refractory patients with active ulcerative colitis (UC), treatment with immunosuppressive agents, such as cyclosporin, azathioprine or 6-mercaptopurin is effective. However, there are patients who fail to respond to these treatment options or who cannot tolerate them. Application of natural interferon-beta (nIFN-beta) may offer an alternative. Following our positive results with nIFN-beta in a previously published open-labeled study, the present study was designed as an extension with the hypothesis that administration of higher dosage of nIFN-beta (1.0 vs. 0.5 MIU) could result in fewer relapse events. PATIENTS AND METHODS: 46 steroid refractory patients with active UC and a mean clinical activity index (CAI) of 13.2 +/- 3.7 (range 9-23) were treated with nIFN-beta in addition to existing basic medication (5-ASA/SASP plus corticosteroids). During an induction period of eight weeks, 18 patients (group A) received 0.5 MIU nIFN-beta daily and 28 patients (group B), 1.0 MIU nIFN-beta daily intravenously as a bolus injection. Patients who achieved complete remission (decrease of CAI to < or = 4) during the induction period received maintenance therapy with nIFN-beta at the same dose level three times a week and corticosteroids were withdrawn. Remissions and maintenance of remissions were evaluated. RESULTS: In both groups, a comparable number of complete remissions occurred during the induction period: in 16 / 18 patients (89 %) in group A and in 24 / 28 patients (86 %) in group B. Duration of maintenance treatment was 60.0 +/- 90.0 weeks in group A and 52.7 +/- 9.6 weeks in group B. Under this treatment, relapses (increase of CAI to > or = 6) occurred in 5 / 16 patients (31 %) vs. 1 / 24 patients (4 %) (p < or = 0.05). Hence, regarding maintaining remissions, the 1.0 MIU group outscored the 0.5 MIU group. Apart from known flu-like side effects, the therapy was well tolerated by all patients in both groups. CONCLUSION: nIFN-beta may be a safe and effective alternative to induce and maintain remissions in patients with steroid refractory active UC. To validate the presented results, its effect has to be investigated in a randomized, placebo-controlled dose-finding trial.

Experimental study on the use of intravenous immunoglobulin (IVIg) in patients with steroid-resistant Crohn's disease.

INTRODUCTION: Treatment of Crohn's disease is based on anti-inflammatory and immunosuppressive therapy. Over time, however, approx. 20 % of patients develop steroid resistance. In these cases, alternative treatment methods are required. Short-term application of intravenous immunoglobulin (IVIg) may serve as an additional alternative. PATIENTS AND METHODS: In 19 steroid-resistant patients (case collection over 15 years) suffering from Crohn's disease (mean CDAI 284.1 +/- 149.8), IVIg therapy with Venimmun, Gamimmun, Octagam, respectively (7 days 10 g/day i. v.) or Sandoglobin (total dose: 72 g or 90 g i. v., respectively, over a period of 8 or 10 days) was applied in addition to basic medication (5-ASA/SASP plus corticosteroids). CDAI according to Best was assessed on a weekly basis starting 3 weeks prior to and ending 4 weeks after completion of therapy. 8 patients could be followed for a longer period. RESULTS: All patients benefited from this treatment and the effectiveness of IVIg therapy could not only be observed during therapy, but also during the four consecutive weeks after therapy. At 4 weeks after therapy, a total of 14 patients (73.7%) reached a clinical remission (CDAI < 150) and 14 patients (73.7%) showed a CDAI decrease of > 100 points. In the 8 patients who could be followed over a longer period of time, a mean remission duration of 20.6 months was observed. Apart from a slight rise in temperature in one patient, no significant side effects occurred. CONCLUSION: In patients suffering from Crohn's disease, IVIg therapy may be applied effectively and with few side effects, however, not as remission maintenance, but as a stopgap treatment during an acute attack with steroid resistance, e. g., until therapy with other immunosuppressive agents becomes effective. To validate our presented results, a prospective, randomised, placebo-controlled trial has to be proposed.

[Acute hepatitis due to kava-kava and St John's Wort: an immune-mediated mechanism?]. / Akute Hepatitis durch Kava-Kava und Johanniskraut: immun-vermittelter Mechanismus?

HISTORY AND CLINICAL FINDINGS: In an otherwise healthy 48-year-old female patient, acute hepatitis with transaminase increase (GOT up to 613 U/l, GPT up to 752 U/l), inconspicuous hepatitis serology findings, negative autoantibody status and negative virus serology was observed after a 10-week long intake of kava-kava (1-3 x 200 mg/day) and St John's Wort (1 x 425 mg/day). Biopsy of the liver showed lobular and portal necroinflammatory activity without indication of cirrhosis. DIAGNOSIS: Due to these findings with proven T-cell activity (lymphocyte typing, neopterin determination) as well as the aetiopathology, this form of hepatitis with histological characteristics of a nutritive/medicinal toxic origin was classified as induced immunologic idiosyncratic hepatitis, possibly in terms of an antibody-negative autoimmune hepatitis. TREATMENT AND CLINICAL COURSE: Discontinuation of the existing medication and simultaneous onset of immunosuppressive combination therapy of cortisone, azathioprine and ursodeoxycholic acid resulted in normalisation of the liver parameters within a period of two months. CONCLUSION: On the one hand, it appears that simultaneous intake of St John's Wort possibly potentiates the toxicity of kavapyrones. On the other hand, an immune-mediated mechanism, induced by kava-kava, cannot be completely excluded in the present case. It must be stressed that in patients with autoimmune hepatitis, precise history of medication intake should also be available.

Randomized, controlled trial with IFN-alpha combined with ribavirin with and without amantadine sulphate in non-responders with chronic hepatitis C.

BACKGROUND/AIMS: Efficacy and safety of interferon-alpha (IFN-alpha)/ribavirin retreatment with or without amantadine sulphate were evaluated in non-responders with chronic hepatitis C. METHODS: Two hundred twenty five consecutive non-responders to previous antiviral treatment(s) with IFN-alpha alone or in combination with ribavirin or amantadine were treated with IFN-alpha 2b 5 MU daily for 4 weeks, 5 MU tiw for 20 weeks, followed by 3 MU tiw for additional 24 weeks combined with ribavirin 1000-1200 mg/d. One hundred fifteen of 225 patients were randomized to receive amantadine sulphate 100 mg bid for 48 weeks. Treatment was discontinued in patients with detectable serum hepatitis C virus (HCV)-RNA at treatment week 24. RESULTS: An overall sustained virologic response with undectable serum HCV-RNA levels was observed in 49/225 patients (22%). Patients infected with HCV-genotype non-1 (P<0.001), low viremia (P=0.011) and only one previous antiviral treatment (P=0.032) were more likely to respond to antiviral retreatment. There was a trend towards higher sustained virologic response rates in patients receiving triple retreatment compared with those treated with IFN-alpha/ribavirin alone (25 versus 18%, P=0.172). CONCLUSIONS: The addition of amantadine was well tolerated and led to an improvement of sustained virologic responses compared with retreatment with IFN-alpha/ribavirin alone, in particular in patients with low baseline viremia.

[Severe exacerbation of chronic hepatitis B during therapy with corticosteroids and lamivudine therapy and successful short-term combination therapy with interferon-beta and interferon-gamma]. / Schwere Exazerbation einer chronischen Hepatitis B unter Therapie mit Kortikosteroiden und Lamivudin und erfolgreiche Kurzzeit-Kombinationstherapie mit Interferon-beta und -gamma.

Following an acute episode of undifferentiated collagenosis/autoimmune disease with joint pain, a 50-year-old female patient with known long-standing chronic hepatitis B was treated orally with corticosteroids (30 mg prednisolone in decreasing doses over a period of six months). During this treatment, exacerbation of hepatitis B and massive flare-up under simultaneous treatment with lamivudine occurred (GOT 530 U/L, GPT 791 U/L). Serology was positive for HBs-Ag and anti-HBc-lgM. HBV-DNA titer was > 400,000 copies/ml in polymerase chain reaction. Considering the increased risk of reactivation of autoimmune phenomena during a six months therapy with interferon-alpha, an intensive combination therapy with interferon-beta and -gamma (2 weeks: 1 x 3 MIU nIFN-beta Fiblaferon i.v.; 3 weeks: 1 x 3 MIU nIFN-beta i.v. plus 1 x 50 microg rIFN-gamma Imukine) was carried out over five weeks. After two months this resulted in a complete viral and biochemical response. During an observation period of twelve months no reactivation of the autoimmune disease occurred.

Intrapericardial instillation of mitoxantrone in palliative therapy of malignant pericardial effusion.

BACKGROUND: Pericardial effusions occurring with pericardial or myocardial metastases often cause serious complications, necessitating temporary or emergency relief by percutaneous pericardiocentesis. However, this often results in recurrences. For long-term therapy success, the intrapericardial instillation of anti-neoplastic agents is an alternative to surgical methods, which are stressful for the patient. Following our positive experiences with mitoxantrone in the treatment of malignant pleural effusions, we applied this substance for the therapy of malignant pericardial effusions. PATIENTS AND METHODS: 16 patients with cytologically verified malignant pericardial effusions (8 with bronchial carcinoma, 7 with carcinoma of the breast, 1 with adenocarcinoma of the stomach) received an intrapericardial instillation of mitoxantrone 1-3 x10-20 mg. Responses were evaluated by echocardiography 30 days after completion of therapy. RESULTS: 12 of 16 patients showed complete remission (no recurrence of a detectable effusion). 3 patients showed a partial remission (recurrence of non-drainage-dependent effusion) (CR + PR = 94%). Within the mean follow-up period of 189 days no recurrences occurred. The rate of side effects was low. CONCLUSION: Intrapericardial instillation of mitoxantrone is a feasible and effective palliative method for the control of malignant pericardial effusions with little strain on the patients, short duration of hospital stay, cytotoxic characteristics of the substance with a correspondingly high rate of response and low side effects.

Amifostine plus erythropoietin in a patient with low-risk myelodysplastic syndrome.

Increasingly, the therapeutic use of hematopoietic growth factors and immunomodulatory agents is under investigation in patients with low-risk myelodysplastic syndrome (MDS). Studies on amifostine therapy-alone or in combination with erythropoietin (EPO)-indicate that long-term treatment is possibly a decisive factor for therapy success. Therefore, we treated an 81-year-old female, transfusion-dependent patient with MDS and refractory anemia (RA) with amifostine and EPO over a period of 2 years. Following a 4-week induction phase of 5 x 500 mg amifostine plus 3 x 10000 IU EPO per week and maintenance therapy of 1 x 500 mg amifostine plus 3 x 10000 IU EPO per week, normal hemoglobin values were reached in week 14. A long-lasting erythroid response could be observed with a reduction of EPO to 2 x 10000 IU and 1 x 10000 IU and, at present, once a week application of amifostine alone (1 x 500 mg). Apart from the 1st week, the treatment was carried out at the outpatient department and was well tolerated by the patient. The patient experienced a good general clinical condition without further need for hospitalization or blood transfusions.

Induction and maintenance of clinical remission by interferon-beta in patients with steroid-refractory active ulcerative colitis-an open long-term pilot trial.

BACKGROUND: The imbalance of pro- and anti-inflammatory cytokines plays an important role in the pathogenesis of inflammatory bowel disease. Shifting this disturbed ratio by means of TNF-antibodies or interferon has been shown to be helpful in treating Crohn's disease and multiple sclerosis, respectively. AIM: This pilot study investigated whether interferon-beta can induce clinical remission in corticoid-refractory ulcerative colitis. METHODS: Twenty-five patients with steroid-refractory active ulcerative colitis (Clinical activity index according to Rachmilewitz: 13.5 +/- 5.2) were treated in an open pilot trial with 0.5 MIU human natural interferon-beta (hn-IFN-beta) i.v. (n=18) or 1 MIU recombinant interferon-beta-1a (r-IFN-beta-1-a) s.c. (n=7) daily with the goal of induction of remission. Subsequent maintenance treatment was carried out for 52.0 +/- 78.8 weeks (range 4-336 weeks) with the same dose, three times per week. RESULTS: Twenty-two of 25 patients (88%) went into remission during induction treatment (hn-IFN-beta 16/18, r-IFN-beta-1a 6/7). Mean time to response was 3.0 +/- 1.3 weeks. Mean length of remission was 13.0 +/- 19.7 months. Only eight of 22 patients in remission relapsed during maintenance treatment. Five of these went into remission again after increasing the dose. Adverse events consisted of slight to moderate flu-like symptoms and slight to moderate hair loss in five of 15 female patients. CONCLUSION: Although this open pilot study included only a small number of patients, the high response rate suggests that interferon-beta may be a safe and effective treatment for steroid-refractory active ulcerative colitis.

Palliation by intratumoral infiltration with natural interferon-beta.

BACKGROUND: Curative approaches to tumor therapy have achieved greater importance through new developments such as cytostatic agents and their combination with other therapy concepts, but for the majority of tumor patients only palliative therapy is possible. Size or location of tumor manifestations can result in severe discomfort for patients, in some cases even in a reduction of functionality. PATIENTS AND METHODS: For the purpose of this study, a total of 55 patients with a variety of advanced malignant diseases nonresponding or progressive under radio- and/or chemotherapy were treated by intratumoral injection of natural human fibroblast interferon (nIFN-beta). nIFN-beta was administered intralesionally 3 times per week for at least 4 weeks at doses of 2-8 MIU, depending on tumor size. Local tumor response was observed over a median follow-up period of 18 weeks. RESULTS: In 37 patients (67%) a complete or partial remission of the local tumor manifestation was achieved. Survival times of these patients were improved compared with those of patients without local tumor remission. 16 patients without significant change of tumor volume benefited from the palliative (extensive analgesic) effect of the nIFN-beta therapy. During treatment, none of the patients showed a progression of the locally treated tumor, even when the basic malignant disease progressed. The side effects of the nIFN-beta therapy were tolerable, and no patient discontinued therapy. CONCLUSION: From these observations, intralesional nIFN-beta therapy of malignant tumors appears to be a useful palliative addition to radio- and/or chemotherapy with the aim of local control of tumor growth.

Are better eye movements an advantage in ball games? A study of prosaccadic and antisaccadic eye movements.

The aim of this study was to compare prosaccadic and antisaccadic eye movements of experts in ball sports and controls. In the prosaccadic and antisaccadic task, subjects made saccades respectively towards and away from a suddenly appearing stimulus. By means of infrared-oculography, we compared horizontal eye movements of experts (n=18) and controls (n=20). Experts had shorter overall saccadic latencies, but significantly shorter latencies occurred only on the antisaccade task, not on the prosaccade task. Our findings seem to support the concept that prosaccades and antisaccades have different underlying mechanisms and that expertise in ball games mainly improves antisaccadic performance in terms of latency and variability.

Ecological relevance of stereopsis in one-handed ball-catching.

The aim of this study was to compare one-handed catching performance between catchers with high (n = 10) and low (n = 10) binocular depth vision or stereopsis. In two sessions of 90 trials, tennis balls were projected at three different velocities towards the subject's shoulder region. Participants with good stereopsis were more successful, although the difference in number of correct catches fell short of significance. More specifically, catchers with low stereopsis made more temporal errors, but no differences in spatial errors. As the velocity of the ball increased, the initiation of the catch was delayed and catching performance decreased. The finding that stereopsis affected timing of the catch challenges the 'monocular tau hypothesis' in the control of interceptive timing, while the velocity effect shows that the act of catching a ball is not initiated at a constant time-to-contact.

Intercepting Moving Objects During Self-Motion.

It is generally assumed that in catching a fly ball, an efficient strategy for dealing with the horizontal component of the ball's trajectory is for the observer to keep the angular position of the ball constant with respect to his head. That strategy is called the constant bearing angle or CBA strategy. Maintenance of angular constancy results in the simultaneous arrival of both observer and ball at the landing spot. The authors analyzed the approach behavior of 26 subjects in a ball-interception task with straight paths for both the subjects and the ball. Subjects moved at a velocity that maintained a close-to-constant horizontal angular position of the ball with respect to the end effector throughout the approach phase rather than a constant bearing angle with respect to their head. Velocity adaptations occurred as a function of the changes in the angular velocity of the ball in such a way that a positive or negative angular velocity was canceled. Thus, an actor following the CBA strategy does not need to know where and when the ball will arrive (i.e., a predictive strategy), because reliance on the CBA strategy ensures that he will make the appropriate adaptations that enable him to arrive at the right place in the right time.

Intercepting moving objects during self-motion: effects of environmental changes.

The purpose of this study was to examine the role of background texture on an interception task during self-motion. Twenty-six participants modulated tricycle speed along one arm of a V-shaped track so as to intercept a ball approaching horizontally on the other arm of the V. Either a plain or a textured background (consisting of contrasting vertical stripes) was used. Velocity modulations occurred so as to keep the angle beta between the direction of heading and the line head-ball constant (constant bearing angle, or CBA strategy), indicating that this observer-environment relation might regulate the approach phase. In the textured condition, participants initially drove faster than predicted by the CBA model and compensated by slowing down in the second half. This is in line with the texture-induced overestimation of the ball velocity and implies that absolute velocity information is also used.

Phase II clinical trial of combined natural interferon-beta plus recombinant interferon-gamma treatment of chronic hepatitis B.

BACKGROUND/AIMS: Alpha-interferon (IFN-alpha) is an effective treatment for chronic hepatitis B but only 25-40% of patients will profit from a long-term beneficial response to the currently recommended schedule of 3-6 MU given 3 times a week for 6 months. Clinical trials are therefore needed to investigate alternative modifications of interferon therapy, including combinations of different antivirals or immune modulators in order to improve the therapeutic approach to chronic hepatitis B infection. In a phase II trial we evaluated whether a combination of natural interferon-beta (nIFN-beta) with strong antiviral activity plus recombinant interferon-gamma (rIFN-gamma) with a predominantly immunomodulatory activity is able to increase the response rate compared to historical controls treated with IFN-alpha in a conventional regimen. METHODOLOGY: Forty patients with chronic hepatitis B were included in this trial of combined interferon therapy at a dosage of 6 MU nIFN-beta during week 1 followed by 3 MU for weeks 2-4 plus rIFN-gamma at a daily subcutaneous (s.c.) injection of 150 microg during the entire 4 weeks of the treatment period. Patients entered the trial on the basis of the following criteria: hepatitis B surface antigen (HBsAG), HBeAG and HBV-DNA positive for at least 6 months, HDV, EBV, CMV, anti-HIV negative, and chronic hepatitis proven on biopsy taken within 4 weeks of entry as well as 6 and/or 12 months after interferon therapy. The final diagnosis and classification of chronic hepatitis has been based on guidelines according to a revised classification of chronic hepatitis (Desmet 1994). The post-treatment follow-up was 12 months. RESULTS: The combined interferon therapy achieved complete responses with seroconversion from HBeAG to anti-HBe and a negative HBV-DNA (dot blot) test, as well as normalization of ALT activity in 15 patients, and partial response with negativation of HBV-DNA concomitant to a decrease in aminotransferase activity to near normal levels in 6 patients. Nineteen patients showed no response to viral markers but showed relief of clinical symptoms as well as pronounced decrease of serumtransaminase activity. Grading of liver biopsies demonstrated an improvement of histologic parameters after the interferon regimen in half of the evaluable patients (n=22). Histological response has been quantified by a reduction in the score of histological activity (HAI-index) from 12.6 before to 7.6 after interferon therapy, and in the inflammation and cellular degeneration score (ICD) from 9.9 to 5.2. Histological response, however, failed to show a consistent correlation with serologic response. This medium-dose combination of interferon-beta and interferon-gamma was tolerated very well by the patients, this good tolerability being explained by tachyphylaxis in response to daily interferon doses. No serious side effects or decompensation of liver function were observed during the 4-week period of therapy or the follow-up, despite the special clinical situation where 60% of the patients included in the study presented with histologically proven cirrhosis (35% of them with clinical manifestation of mildly decompensated cirrhosis). CONCLUSIONS: This short-term regimen of combined nIFN-beta + rIFN-gamma therapy in patients with chronic hepatitis B proved to be equieffective to long-term treatment with interferon-alpha and combines high clinical tolerability with good practicability, as it can be administered on an in-patient basis, ensuring close patient monitoring.

[Tuberculous anal fistula in acquired immunologic deficiency syndrome]. / Tuberkulöse Analfistel bei erworbenem Immundefektsyndrom.

We report here on a 36-year old, HIV-positive patient, who was sent to hospital with an anal fistula. A short time later during the course of an extensive diagnosis the anal fistula was recognized as an extrapulmonary manifestation of a miliary tuberculosis stemming from an immunodeficiency syndrome. A rapid conversion of the sputum, a normalization of the radiological findings and the absence of relapse are the results of the classic systemic fourfold therapy with myambutol, isoniazid, rifampicin and streptomycin. The danger of overlooking the fact that an anal fistula can be the clinically primary manifestation of a tuberculosis and the problems of a mixed infection within the scope of the acquired immunodeficiency syndrome are discussed. Tuberculosis as a frequent complicating infection of HIV-positive patients--often diagnosed some time before the AIDS-infection as in our patient--can be successfully cured by a high dose of intravenous pharmacotherapy, even when additional complications (parasitic stomatitis, increasing deterioration of the immunological parameters) are present. In order to show the large spectrum of the problems involved in the diagnosis, the therapy and the course of the active acquired immunodeficiency syndrome, we have focused here on the detailed description of the case report.

Cryoglobulinemia: a complication of infectious disease.

We report on a 23-year-old male patient with general weakness, subfebrile temperatures, and arthralgia. The first symptoms were observed some months after a severe cytomegalovirus mononucleosis-gastroenteritis. High titers of cryoglobulins suggested an autoimmunological process. This case is interesting because of the association between cytomegalovirus infection and cryoglobulinemia. In conclusion, the differential diagnosis of autoimmune disease should be considered in the course of viral infections.

Lipid peroxides in the polychemotherapy of cancer patients.

There is evidence that a variety of anticancer drugs exert their cytotoxic activity by a free-radical-mediated mechanism. These drugs include anthracyclines such as adriamycin, daunorubicin, 4-epi-adriblastin as well as bleomycin, procarbazine, vincristin, cyclophosphamide, etoposide and mitomycin C. The aim of this study was to investigate whether cancer patients who underwent polychemotherapy (n = 44) show more signs of oxidative stress in plasma than a group of healthy controls (n = 52). As an index of free radical generation, plasma concentrations of thiobarbituric-acid-reactive substances (TBARS), well-accepted as markers for oxidative stress, were determined by fluorometric detection after separation by high-performance liquid chromatography. In 12 cases, the TBARS were measured both before and after a chemotherapy course. After chemotherapy, 10 of 12 patients showed a marked increase in plasma TBARS concentration compared to values measured before therapy [9.02 +/- 1.84 nmol/ml (n = 12) vs. 11.58 +/- 2.49 nmol/ml (n = 12); p = 0.002, t-test for paired observations]. Tumor patients in general had significantly larger amounts of TBARS in plasma in comparison with a control group [mean 11.88 +/- 3.51 nmol/ml (n = 44) vs. 7.51 +/- 2.14 nmol/ml (n = 52); p < 0.001, t test]. Our results are evidence that repetitive polychemotherapy with radical-generating compounds may exceed the antioxidative capacities of cancer patients and may lead to oxidative stress.

Interleukin-2 followed by fluorouracil and folinic acid in refractory colorectal cancer--results of a clinical phase II study.

In a clinical phase II study, 23 patients with progressive metastatic colorectal cancer and failure after first-line chemotherapy with fluorouracil (5-FU) and folinic acid (FA) were treated with a 5-day continuous infusion of recombinant interleukin-2 (IL-2), 3 x 10(6) cetus U/m2/d, followed after a rest period of 2 days by 5-FU, 600 mg/m2/d, and FA, 300 mg/m2/d over an additional 3 days. After two to four treatment cycles, eight of 22 evaluable patients (36%) revealed antitumor responses, with three partial remissions and five minor responses or stable disease. Side effects consisted most frequently of fever, nausea and vomiting, an elevation of liver enzymes, hypotension, and skin toxicity, and required a 50% reduction of IL-2 dose in 17 of 71 treatment courses (24%). In four of the 23 patients (18%), treatment had to be stopped completely. These data indicate a significant antitumor activity of IL-2 combined with 5-FU/FA therapy in chemotherapy-resistant colorectal cancer. Hence, in spite of a substantial treatment-related toxicity, further studies are warranted to substantiate these findings and to elucidate the underlying mechanisms of the IL-2-5-FU/FA combination therapy.