M.E. Heim

Prognostic factors of advanced colorectal cancer patients

The cooperative oncology group for Chemotherapy of Gastrointestinal Tumors (CGT) retrospectively examined 139 patients with metastatic colorectal cancer for prognostic factors. Clinical characteristics, tumor parameters, and blood parameters were investigated for prognostic explanation of survival from the start of chemotherapy for the advanced disease. A combination of a univariate regression and a multivariate step down procedure with Coxs regression model led to the identification of performance status, sex, white blood count and, to a lesser degree, blood sedimentation rate and albumin as important prognostic factors. Based on these variables an individual risk score was calculated for each patient.

Clinical Experience with Levonantradol Hydrochloride in the Prevention of Cancer Chemotherapy-Induced Nausea and Vomiting

Abstract: Reports suggesting that Δ9‐tetrahydrocannabinol (THC) had a potent antiemetic effect in patients treated with cancer chemotherapeutic agents led to the synthesis of other cannabinol derivatives with possibly less side effects. We report here our initial observations with the antiemetic levonantradol in 12 patients with advanced solid tumors receiving cytotoxic polychemotherapy. All patients had a history of vomiting and nausea without successful treatment with standard antiemetic drugs in previous, identical chemotherapy cycles. No other antiemetic or psychoactive drugs were given. Patients received 1 mg levonantradol i.m. 2 hours before as well as 2 and 6 hours after cytotoxic treatment. When compared to the last course of chemotherapy with alternate antiemetic drugs, we found that 11/12 patients had less nausea and vomiting when treated with levonantradol. 8/12 Patients considered the antiemetic treatment with levonantradol better than the one given before. The following side effects were observed: 4 patients complained of pain and local irritation after injection. 2 patients showed a fall in blood pressure, especially orthostatic hypotension. 8 patients complained of sedation and drowsiness. 7 patients experienced psychic side effects, such as decrease of vigilance and reaction, altered sense of timing, body image distortions and even depersonalization. Levonantradol is a potent antiemetic drug but its applicability, especially in outpatients, may be complicated by a high incidence of side effects.

Clinical Studies with Budotitane, a New Non-Platinum Metal Complex for Cancer Therapy

The new antitumor-active transition metal complex diethoxybis(1-phenylbutane-1,3-dionato)tita- nium(IV) (INN Budotitane, DBT) has demonstrated antitumor activity in several experimental tumor models. The cytotoxic activity of DBT in the AMMN-induced autochthonous colorectal carcinoma in the rat appeared especially promising. In the preclinical toxicity studies, liver toxicity, mild nephrotoxicity, but no myelosuppression was observed.

Lebensqualität von Karzinom-Patienten unter Chemo- und Radiotherapie

156 Patienten mit fortgeschrittenen Bronchial- und Gastrointestinal-tumoren, die sich einer palliativen Chemo- und Radiotherapie unter-zogen, wurden in einer prospektiven Studie zur Veranderung ihrer Lebensqualitat unter Therapie untersucht. Als Mesinstrumente dien-ten ein Fragebogen (68 Fragen), eine lineare Analog-Skala und der Karnofsky-Index, die dreimal im Verlauf der Therapie zur Auswer-tung kamen. Die Auswertung des Fragebogens erbrachte als wichtig-sten Punkt eine Verbesserung des psychischen Befindens selbst bei Zunahme der Nebenwirkungen, wenn es bei den Patienten zu einer Tumorremission kam. Entwickelte sich jedoch eine Tumorprogres-sion, zeigte sich eine deutliche Mehrbelastung durch Nebenwirkungen und eine Verschlechterung des psychosozialen Befindens. Diese Ergebnisse bestatigen auch die Untersuchung der linearen Analog-Skala fur die tumorprogredienten Patienten. Der Karnofsky-Index zeigte eine hohe Korrelation fur die Beurteilung von krankheitsbezo-genen Inhalten und der Aktivitat des Patienten. In dieser Studie wird die Abhangigkeit von Therapieeffekt und Befinden des Patienten aufgezeigt. Es erscheint daher wichtig, Methoden zur Erfassung der Lebensqualitat in die Beurteilung onkologischer Therapien mit einzu-beziehen.

Phase I–II trial of doxifluridine (5′DFUR) administered as long-term continuous infusion using a portable infusion pump for advanced colorectal cancer

Doxifluridine, a new fluoropyrimidine analog, was administered to 21 patients with advanced colorectal carcinoma. The starting dose was 1.0 g/m2 given over 24 h for 90 consecutive days as a continuous infusion. Due to severe skin reactions (hand-foot syndrome), the dose was reduced stepwise to 0.75 g/m2/day. Twenty patients were evaluable for efficacy, one had an early non-toxic death. Seven out of 20 (35%) showed a partial response; disease stabilization was observed in 10 patients (50%) and three showed progressive disease after 3 months of treatment. All 17 patients who achieved a partial response or a stabilization of disease were treated until progressive disease was documented and some had therapy up to 46 weeks. Toxicity was minimal and mainly defined as hand-foot syndrome which occurred in 50% of the patients of whom three experienced severe reaction. There was no myelosuppression, renal or liver dysfunction, no cardiac alterations and only one patient experienced severe dizziness. Doxifluridine is active in advanced colorectal carcinoma when the drug is given as a continuous infusion for 90 consecutive days at a daily dose of 0.75 g/m2.

5-Fluorouracil, 4-Epidoxorubicin, and Mitomycin C (FEM) Combination Chemotherapy for Advanced Gastric Carcinoma. A Phase-II Trial by the “Chemotherapiegruppe Gastrointestinaler Tumoren (CGT)”

In a phase-II-trial 40 patients with advanced gastric cancer were treated with 5-fluorouracil, 4-epidoxorubicin, mitomycin C (FEM) combination therapy. Twenty-five out of 30 patients with measurable disease were evaluable for response after 8 weeks of treatment. Seven patients achieved a partial remission (PR), suggesting a response rate of 28%. Ten patients had no change (NC) and 8 patients showed progression (P). The median time to progression for patients with PR was 7.2 months and for patients with NC 6.3 months. Median survival time for all patients was 5.3 months, for patients with PR and NC 9.9 months. WHO grade 3 toxicity appeared in 3% (WBC and nausea/vomiting) and 15% (alopecia) of patients. The data suggest that this regimen is not more active, but is better tolerated than the original FAM schedule. Therefore it seems suitable for out-patient treatment, for elderly patients and for those who cannot be treated by more aggressive drugs.

Consultation Program for Patients with Cancer-Related Fatigue: A Systematic Evaluation of the Experiences of the Bavarian Cancer Society

a Institut fur Tumor-Fatigue-Forschung, Emskirchen, Germany; b AG Tumor-Fatigue in der BKG e.V., Munich, Germany; c Deutsche Fatigue Gesellschaft e.V., Cologne, Germany; d Krebsberatungsstelle am Tumorzentrum Munchen in Kooperation mit der Bayerischen Krebsgesellschaft e.V., Munich, Germany; e Rotkreuzklinikum Munchen, Munich, Germany; f Gesundheitszentrum Bodensee, Klinik Sokrates, Guttingen, Switzerland; g Bayerische Krebsgesellschaft e.V., Munich, Germany; h Psycho-Onkologie Medizinische Klinik III und CCC LMU, Klinikum der LMU-Groshadern, Munich, Germany; i Facharztzentrum Furstenfeldbruck, Furstenfeldbruck, Germany; j Klinik Herzoghohe, Bayreuth, Germany; k Praxis fur Psychosomatische Medizin und Psychotherapie, Psychoonkologie, Traumatherapie, Wangen, Germany; l Zentrum fur Klinische Studien, Universitatsklinikum Regensburg, Regensburg, Germany

Combination of Recombinant Interferon Alpha-2A and Vinblastine in Advanced Renal Cell Cancer

Experimental results suggest synergistic activity of interferon with different cytotoxic agents, including vinblastine. Both interferon and vinblastine have shown synergistic activity against renal cell carcinoma in the human stem cell assay. In this multicenter phase II study, patients with documented advanced renal cell carcinoma were treated with interferon alpha-2a at a dose of 18 x 10(6) IU i.m. 3 days per week and vinblastine 0.1 mg/kg body weight i.v. every 3 weeks. Combination therapy was given for 6 months except patients with progressive disease. We observed 6/34 (17.6%) partial remissions and 16/34 (47%) no changes. Five out of six responses were seen in pulmonary metastases with a median response duration of 10 months and a median survival for the responders of 17 months. A dose reduction because of interferon toxicity was necessary in 60% of the treated patients. The main side effects were fever and influenza-like symptoms of different intensity in 70% of the patients, which decreased during the treatment periods. This trial demonstrates modest but definite antitumor activity of the combination of interferon alpha-2a/vinblastine. In comparison with single agent therapy we did not observe improved remission rates for the combination treatment.

Combined Modality of Radiation and Chemotherapy for the Treatment of Gastric Carcinoma

The results of combined radiation and chemotherapy for the treatment of gastric carcinoma are reviewed. A small amount of postoperative adjuvant combined treatments of the curatively resected gastric carcinoma was performed which do not suggest any advantage of treatment compared to observation. For locally advanced and unresectable gastric carcinoma 5-fluorouracil or ftorafur was administered simultaneously to local irradiation in several phase-II studies. The response rates of 37%-58% and one year survival of 45%-72% do not suggest an advantage of combined modality compared to the one way treatment. The FAM, FAMe or FAB regimen was also used and obviously do not improve the results of combined modality treatment. A small but well conducted prospective randomized trials compared radiotherapy with and without chemotherapy or chemotherapy with and without radiotherapy. Recent results from different cooperative groups failed to improve the treatment results in terms of response and survival.

Dose Escalation and Split Course of 4-Epidoxorubicin in Combination Chemotherapy (FEM II) of Advanced Gastric Carcinoma

In a phase II trial 46 patients with advanced gastric carcinoma were treated with FEM combination chemotherapy (5-fluorouracil, 4-epidoxorubicin and mitomycin C) in which 4-epidoxorubicin was administered by escalated dose and split course (FEM II). Twenty-nine patients with measurable disease were evaluable for response. One complete remission and 7 partial remissions were achieved, suggesting an overall response rate of 28%; 2 minimal responses (7%) and 9 patients with no change were observed (31%); 10 patients had tumor progression (34%). Median survival time for all patients was 6.2 months, for patients with CR + PR + MR 16.2 months, for patients with no change 8.4 months, and with tumor progression 3.5 months. WHO grade 2 and 3 leukopenia appeared in 6%, thrombocytopenia in 0% and alopecia in 27% of the patients after the first cycle. Nausea and vomiting grade 2 and 3 were seen in 21%. Comparing these results with our earlier data achieved with FEM I, FEM II showed a tendency towards better response and survival, and subjective toxicity (nausea/vomiting) was significantly reduced. Therefore, in our opinion FEM II is preferable for practical use.