Influence of comorbidity, age and performance status on treatment efficacy and safety of cetuximab plus irinotecan in irinotecan-refractory elderly patients with metastatic colorectal cancer.

BACKGROUND: We investigated the influence of comorbidity, Eastern Cooperative Oncology Group (ECOG) performance status and age on the efficacy and safety profile of cetuximab and irinotecan in elderly irinotecan-pretreated patients with mCRC. METHODS: 497 patients with mCRC were entered in the database of this non-interventional study (NIS). Comorbid conditions were recorded. RESULTS: A total of 247 and 250 patients aged <65 and >65 years, respectively, with a median age of 66 y were documented; 78% of the patients showed a reduced ECOG status. Grade III/IV toxicities occurred in 18% of patients without any difference between age groups although older patients had more comorbidities with a higher Charlson Comorbidity Index (CCI) (p = 0.002). Skin rash was strongly related to response (p = 0.006). Age, line of therapy, ECOG, gender and CCI had no influence on response. The objective response rates were similar: 38.1% for age <65 years versus 36.4% for age >65 years (p = 0.57). Progression-free survival (PFS) did not differ between patients 18-65 years (6.0 months) and patients >65 years (6.2 months; p = 0.99). Only PS had a negative impact on PFS (hazard ratio (HR): 0,499; 95% confidence interval (CI) 0.34-0.72; p=0.002), whereas the presence of skin toxicity (grade>1) influenced PFS and response rate (RR) positively (HR: 2.04; 95% CI, 1.6-2.6; p<0.001). CONCLUSIONS: Only PS and age had a negative influence on PFS irrespective of CCI or age. There were no significant differences in response rate and safety profile for elderly patients when treated with cetuximab and irinotecan. Comorbidities and age had no influence on efficacy or toxicity.

Cetuximab-based therapy in elderly comorbid patients with metastatic colorectal cancer.

BACKGROUND: Clinical trials under-represent patients (pts) >65 years. Non-interventional studies (NISs) help to evaluate therapies in daily practice. This NIS evaluates efficacy and safety of cetuximab in combination with chemotherapy in metastatic colorectal cancer (mCRC) pts aged >65 years vs ≤ 65 years. METHODS: A total of 657 pts were recruited into the NIS and analysed applying descriptive statistics and χ(2) or Fisher's exact test. RESULTS: A total of 309 and 305 pts aged ≤ 65 and >65 years, respectively, were documented; 80% showing a reduced ECOG status of 1-2 and 95% having received at least one palliative treatment. Cetuximab was combined with irinotecan according to approval status. Grade III/IV toxicities occurred in 20% of pts without any difference between age groups although the older pts had significantly more pre-existing comorbidities (P=0.001). A total of 64.2% of the pts developed skin rash, which was strongly related to response (P<0.0002) without any difference between age groups (P=0.34). The objective response rates were 37.9% for ages 18-65 years vs 35.4% for >65 years. Progression-free survival (PFS) did not differ between pts 18-65 years old (6.5 months) in comparison with pts >65 years (7.0 months). In a multivariate analysis only ECOG status had a negative impact on PFS (HR: 0,675; 95% Cl, 0.53-0.87; P=0.0019). CONCLUSION: This NIS reports one of the largest mCRC collectives >65 years and reduced performance status. Cetuximab has a similar efficacy and safety profile for pts aged ≤ 65 and >65 years.

[Treatment of chemotherapy-induced nausea and vomiting with 5-hydroxytryptamine type 3 receptor antagonists]. / Antiemetische Therapie mit 5-HT(3)-Antagonisten in der onkologischen Praxis.

BACKGROUND AND OBJECTIVE: 5-hydroxytryptamine 3 (5-HT3) receptor antagonists have proved to be highly efficacious in the prevention and treatment of chemotherapy-induced nausea and vomiting (CINV). However, several questions remain concerning the relative efficacy of various approved anti-emetics, especially with respect to dosage, duration and timing of administration, as well as differences in toxicity profiles. Thus it seemed appropriate to assess the current therapeutic results in routine daily practice, when applying antiemetic therapy according to established guidelines. PATIENTS AND METHODS: Within LINO e.V., a group of medical oncologists in private ambulant practice (LINO: Association of private-practice medical oncologists in Bavaria), a total of 738 cycles of moderately or highly emesis-inducing chemotherapy were randomly assigned to three treatment options: (1)granisetron 1 mg (GRA1). (2) 3 mg (GRA3), and (3) ondansetron 8 mg (OND8), each combined with 8 mg dexamethasone. Incidence and severity of acute (day 1) and delayed CINV (day 2-5) and the subjective assessment of efficacy were documented on questionnaires filled in by the patients. RESULTS: All of the three regimens adequately prevented vomiting in the majority of the patients. However, all measured effects showed an uniform trend towards slightly decreased efficacy with 8 mg of ondansetron. These differences were predominantly detected with respect to delayed CINV on days 2 to 5, especially after chemotherapy with anthracyclin/cyclophosphamide combination therapy. CONCLUSION: Granisetron, at two different dosage regimens, and ondasetron showed adequate reduction in chemotherapy-induced nausea and vomiting, but ondansetron worked slightly less so.

[Organisation of studies]. / Organisation von Studienteilnahmen in der hämatoonkologischen Praxis.

Haemato-oncological studies in private practices for haematology and oncology have been identified as an important instrument for quality assurance in the treatment of haemato-oncological patients. As the organisational structures of private practices for haematology and oncology are usually highly complex the inclusion into studies needs a high motivation and binds resources. Workflow was observed in four private practices for haematology and oncology. With this data, suggestions for a common workflow model for study inclusion in private practices were elaborated and are discussed in this article. A common workflow-model of study inclusion for private practices is illustrated in two flow charts. If patients are to be successfully included in studies, additional structures and resources have to be implemented. Beyond this the necessary steps for study inclusion must be incorporated into the everyday routine of the practices.

[Ambulatory palliative treatment in oncology. Medical and psychosocial care of tumor patients in the advanced stadium of the disease]. / Ambulante onkologische Palliativbehandlung. Medizinische und psychosoziale Betreuung im fortgeschrittenen Stadium eines Tumorleidens.

Many patients with terminal cancer would prefer to receive care at home. Frequently, however, socio-economic or familial constraints make this impossible, although from the medical point of view there might be no objections, even when the late stage of the disease is associated with certain complications. However, the preconditions must first be defined and agreed when the patient and relatives are making the necessary preparations--as far as possible jointly with a team comprising family doctor, oncologist and nursing service. Binding agreements among all those involved are required to ensure that in difficult situations the patient and his family receive the support they need. A number of common medical problems met with during palliative treatment, such as diarrhea, constipation, pleural effusion, etc. are described.

[Management of tumor patients in oncology-oriented practices]. / Betreuung von Tumorpatienten in onkologischen Schwerpunktpraxen.

Up until a few years ago, the diagnosis and treatment of tumor patients was the domain of the hospital. In recent years, however, ever more "oncologically-oriented practices" have been established with the aim of providing specific care to tumor patients. In these practices both diagnostic evaluation and most forms of chemotherapy can be carried out. The advantages to the patient in the care of such practices are constancy of the doctor/patient relationship, faster diagnostic evaluation and provision of results, and better preservation of the patient's domestic milieu through less hospitalization.

Chemotherapy of invasive thymoma. A retrospective study of 22 cases.

The authors report on combination chemotherapy in 22 patients (seven men, 15 women; age 20-67, median 38.5 years) with incompletely resected invasive thymoma. Twelve of 22 patients have had prior radiotherapy of the tumor (four of 12 local failure, eight of 12 remote metastases). By subsequent chemotherapy five of 12 obtained complete remission (CR). One of them died by relapsed tumor, another by an intercurrent infection. At 5 years after diagnosis the survival rate of the 12/22 patients was 33% (Kaplan-Meier). Ten of 22 patients received chemotherapy as primary treatment of incompletely resected thymoma. Four of 10 obtained CR. One of them was lost during follow-up, the others received adjuvant irradiation of the mediastinum and are free of disease. Two of ten obtained partial remission (PR), but relapsed within 6 months after chemotherapy. At 3 years after diagnosis the survival rate of the 10/22 patients was 34%. Thirteen of 22 patients received cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP/bleomycin as first chemotherapeutic regimen. Five of them achieved CR. Cyclophosphamide, vincristine, and prednisone (COP) or COP plus procarbazine (COPP) was administered to six of 22. Three of them obtained a CR and one a PR. In an alternating manner COPP and Einhorn regimens were given to two of 22, one of which had a CR. In one of 22 the doxorubicin, bleomycin, cisplatin, prednisone (BAPP) regimen was followed by a PR. The authors conclude that combination chemotherapy is effective in the first-line postsurgical treatment of incompletely resected thymoma and also in the treatment of local or metastatic relapses after radiotherapy.

[Successful chemotherapy of a metastatic malignant thymoma]. / Erfolgreiche Chemotherapie bei metastasiertem malignem Thymom.

An epithelial thymoma was diagnosed in June 1978 in a 42-year-old-woman. The tumor had already encased the great vessels and infiltrated into sternum and both lungs. Full remission followed local radiotherapy with 25 Gy. In February 1979, intrapulmonary and bony metastases were discovered. After 12 cycles of the COP schema after Bagley (cyclophosphamide, vincristine and prednisolone) full remission was again achieved, which still persists. This case and other published results suggest that cytostatic combinations are often successful in the treatment of advanced malignant thymoma and could be an alternative to the present practice of radiotherapy of inoperable or incompletely resectable thymomas.

Treatment of non-hodgkin's lymphoma of low-grade malignancy with human fibroblast interferon.

10 patients with advanced non-Hodgkin's lymphoma of low malignancy were treated with partially purified HulFN-beta. They received daily i.v. infusions of 4.5 X 10(6) IU for 4 weeks, followed by 9 X 10(6) IU daily for 2 weeks. Patients with stable disease during this period received consolidation therapy with 4.5 X 10(6) IU three times per week for a maximum of 20 weeks. Six out of 10 patients had progressive disease after the initial 6 week treatment and 4 had stable disease. Two of the latter developed progressive disease during consolidation therapy, one had a complete remission of minimal bone marrow involvement, and one was in partial remission with a loss of bone marrow infiltration but unchanged lymph node enlargement.

[Adriamycin and autologous bone marrow transplantation. Preclinical studies in dogs (author's transl)]. / Adriamycin und autologe Knochenmarktransplantation. Vorklinische Studien am Tiermodell (Hund)

We investigated the toxicity of adriamycin (ADM) in dogs with regard to autologous bone marrow transplantation (BMT). Gastrointestinal toxicity limited the dose of ADM in single administration (3.0 mg/kg) and chronic cardiotoxicity in repeated administration (9 X 1.5 mg/kg every two weeks). The recovery of hemopoiesis was complete within 25 days after single and repeated doses of ADM as indicated by the restoration of blood counts and concentration of hemopoietic precursors (CFUc) as well as proliferate activity of bone marrow. At this time bone marrow was obtained and reinfused after total body irradiation (TBI) with 10 Gy. Single and repeated doses of 1.5 mg/kg ADM did not delay recovery of blood counts after autologous BMT as compared to transplantation of untreated marrow - in contrast a single dose of 3.0 mg/kg ADM did. Our results indicate that toxicity of ADM is not influenced by autologous BMT. Previous shorter therapy with conventional doses of ADM does not preclude autologous BMT.

[Culture of mononuclear cells from patients with aplastic anemia in diffusion chambers (author's transl)]. / Kultur mononukleärer Blutzellen von Patienten mit aplastischer Anämie in der Diffusionskammer.

The growth of mononuclear human peripheral blood cells from five patients with aplastic anemia (AA) was tested in diffusion chambers over a period of 13 days. Considerable differences were seen in the total cell number compared with controls. The total cell number of three patients with AA was markedly lower than in the control group (eight controls). The differentiation of the cells showed considerable differences in the growth patterns of the lymphocytes and in granulopoiesis; in three of five patients with AA no granulopoiesis was observed.

Growth of the Reh cell line in diffusion chambers. Evidence for differentiation along the T- and B-cell pathway.

Cells of the Reh line, originally derived from an ALL of the 'Non-T, Non-B' type were cultured in diffusion chambers implanted intraperitoneally into perirradiated CBA mice. At different intervals over a period of 20 d changes in surface characteristics were examined by labelling the cells with AcALLG, ATCG as well as with polyvalent AIg. The evaluation was performed by using direct immunofluorescence. In addition, the ability to form rosetts with SRBC, AET-treated sheep erythrocytes, mouse red blood cells and EoxAC was tested. On day 0 of the diffusion chamber culture the cells only carried cALLA, and no rosette formation was observed. In the course of the diffusion chamber culture the cells unequivocally developed T-cell antigen, and in 1 of 2 experiments they further acquired a receptor for forming AET- and E-rosettes. Conversely, in the other experiment a receptor for mouse red blood cells was detected in a considerable portion of the cells. Our data show that the rather undifferentiated Reh line cells in vitro are able to develop features of mature T-cells and attributes of early B-cells during the diffusion chamber culture. In vitro they apparently retain a bivalent potentiality of lymphatic maturation. The diffusion chamber system proves to be a suitable tool for promoting differentiation in these cells.