Background: The optimal treatment of elderly patients with Hodgkin's lymphoma (HL) is still a matter of debate. Since many of these patients receive combined modality treatment, we evaluated the impact of different radiation field sizes, that is extended-field (EF) or involved-field (IF) technique when given after four cycles of chemotherapy.Patients and methods: In the multicenter HD8 study of the German Hodgkin Study Group, 1204 patients with early-stage unfavorable HL were randomized to receive four cycles of chemotherapy followed by either radiotherapy (RT) of 30 Gy EF + 10 Gy to bulky disease (arm A) or 30 Gy IF + 10 Gy to bulky disease (arm B). A total of 1064 patients were assessable for the analysis. Of these, 89 patients (8.4%) were 60 years or older.Results: Elderly patients had a poorer risk profile. Acute toxicity from RT was more pronounced in elderly patients receiving EF-RT compared with IF-RT [World Health Organization (WHO) grade 3/4: 26.5% versus 8.6%)]. Freedom from treatment failure (FFTF, 64% versus 87%) and overall survival (OS, 70% versus 94%) after 5 years was lower in elderly patients compared with younger patients. Importantly, elderly patients had poorer outcome when treated with EF-RT compared with IF-RT in terms of FFTF (58% versus 70%; P = 0.034) and OS (59% versus 81%; P = 0.008).Conclusion: Elderly patients with early-stage unfavorable HL generally have a poorer risk profile and outcome when compared with younger patients. Treatment with EF-RT instead of IF-RT after chemotherapy has a negative impact on survival of elderly patients and should be avoided.

In contrast to younger patients, the prognosis of elderly patients with advanced Hodgkin's disease (HD) has not improved substantially over the last 20 years. We thus carried out a prospectively randomized study (HD9(elderly)) to compare the BEACOPP regimen in this setting against standard COPP-ABVD. Between February 1993 and 1998, 75 patients aged 66-75 years with newly diagnosed HD in advanced stages were recruited into the HD9 trial as a separate stratum (HD9(elderly)). Patients were assigned to eight alternating cycles of COPP and ABVD or eight cycles of BEACOPP in baseline doses. Radiotherapy was given to initial bulky or residual disease. In total, 68 of 75 registered patients were assessable: 26 were treated with COPP-ABVD and 42 with BEACOPP baseline. There were no significant differences between COPP-ABVD and BEACOPP in terms of complete remission (76%), overall survival (50%) and freedom from treatment failure (FFTF) (46%) at 5 years. At a median follow-up of 80 months, a total of 37 patients died: 14/26 patients (54%) treated with COPP-ABVD and 23/42 patients (55%) with BEACOPP. Two patients (8%) treated with COPP-ABVD and nine patients (21%) treated with BEACOPP died of acute toxicity. Hodgkin-specific FFTF at 5 years was 55% after COPP-ABVD and 74% after BEACOPP (P=0.13). Thus, there are no differences in survival between these regimens in elderly patients.

BACKGROUND:The purpose of this study was to compare the efficacy of the hybrid chemotherapeutic regimen COPP/ABV/IMEP (cyclophosphamide-vincristine-procarbazine-prednisone-doxorubicin-bleomycin-vinblastine-ifosfamide-methotrexate-etoposide) (CAI) with that of the standard regimen COPP/ABVD (COPP/ABV, dacarbacine) (CA) in the treatment of advanced-stage Hodgkin's disease (HD). PATIENTS AND METHODS:Between January 1988 and January 1993, 588 eligible patients with HD in stages IIIB and IV were randomly assigned to a treatment or control group. The treatment group received four cycles of CAI over a complete cycle duration of 43 days. The control group received four cycles of CA over 57 days. Both groups then received consolidating radiotherapy. RESULTS:Five hundred and eighty-four patients were suitable for arm comparison. Patients in each group were similar in age, sex, histological subtype and clinical risk factors. Complete remission rates, overall survival and freedom from treatment failure at 7 years were similar for the two groups: 77% versus 78%, 73% versus 73% and 54% versus 56% for CAI and CA, respectively. Differences in acute chemotherapy-related toxicity were significant, however. Prognostic factor analysis confirmed the relevance of the International Prognostic Index and revealed that stage IVB, low hemoglobin, low lymphocyte count, high age and male gender were associated with a poor prognosis CONCLUSION:The rapidly alternating hybrid CAI did not give superior results when compared with the standard regimen CA in advanced-stage HD.

Purpose: This multicenter pilot study assessed the feasibility and efficacy of a time-intensified bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) regimen given in 14-day intervals (BEACOPP-14) with granulocyte colony-stimulating factor (G-CSF) support in advanced Hodgkin’s lymphoma. Patients and Methods: From July 1997 until March 2000, 94 patients with Hodgkin’s lymphoma stage IIB, III, and IV were scheduled to receive eight cycles of BEACOPP-14. Consolidation radiotherapy was administered to regions with initial bulky disease or residual tumor after chemotherapy. Results: All patients were assessable for toxicity and treatment outcome. Eighty-six patients received the planned eight cycles of BEACOPP-14. Consolidation radiotherapy was given in 66 patients. Chemotherapy could generally be administered on schedule. Dose reductions varied among drugs but were generally low. Acute toxicity was moderate, with World Health Organization grade 3/4 leukopenia in 75%, thrombocytopenia in 23%, anemia in 65%, and infection in 12% of patients. A total of 88 patients (94%) achieved a complete remission. Four patients had progressive disease. At a median observation time of 34 months, five patients have relapsed, one patient developed a secondary non-Hodgkin’s lymphoma, and three deaths were documented. The overall survival and freedom from treatment failure rates at 34 months were 97% (95% confidence interval [CI], 93% to 100%) and 90% (95% CI, 84% to 97%), respectively. Conclusion: Acceleration of the BEACOPP baseline regimen by shortening cycle duration with G-CSF support is feasible and effective with moderate acute toxicity. On the basis of these results, the German Hodgkin’s Lymphoma Study Group will compare the BEACOPP-14 regimen with BEACOPP-21 escalated in a prospective multicenter randomized trial.

The BEACOPP (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, and prednisone) regimen, a rearranged and accelerated version of the standard COPP/adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy, has been shown to be effective and safe in a previous pilot study for advanced stage Hodgkin’s disease (HD). The present study aimed to determine a maximum practicable dose of three drugs, ie, etoposide, adriamycin, and cyclophosphamide, for which acute toxicities were acceptable and to assess the feasibility of the escalated scheme. Sixty untreated patients with advanced stage HD were enrolled in this study. Radiotherapy was given in 44 patients (73%) after chemotherapy to initial bulk lesions and residual disease. Granulocyte-colony stimulating factor (G-CSF) was given from day 8 to prevent prolonged neutrocytopenia and severe infections. The intended doses of adriamycin, etoposide, and cyclophosphamide in the BEACOPP schedule could be substantially escalated: adriamycin from 25 to 35, cyclophosphamide from 650 to 1,200, and etoposide from 100 to 200 mg/m2. The major toxicities were leukocytopenia and thrombocytopenia with considerable heterogeneity between individual patients. Of 60 patients, 56 (93%) achieved a complete remission (CR). At a median observation of 32 months, the rates of survival and freedom from treatment failure (FFTF) were estimated to be 91% (95% confidence interval 83% to 99%) and 90% (82% to 98%). These results show that a moderate dose escalation of adriamycin, cyclophosphamide, and etoposide of the baseline BEACOPP regimen is feasible. The escalated BEACOPP regimen shows very encouraging results in advanced stage HD and is now being compared in a randomized phase III study with BEACOPP at baseline dose level.

Background: Nephroblastoma is a common disease in childhood, accounting for 20% of pediatric neoplasms. However, in adults it is rare, only episodical reports are available. No standard treatment schedules do exist. Case report: We present a 41-year-old patient suffering from this condition. In addition, the case showed some unusual features. The latent period between tumor nephrectomy and metastatic disease has been long, the site of the metastases (liver, bowel) rather uncommon. Raised ACTH levels with a secondary hypercortisolism were found, resolving after one course of chemotherapy in spite of tumor persistence. Aggressive polychemotherapy resulted in a 'no change' situation. On obvious progress transarterial chemo embolization was performed, again stabilizing tumor size for further 8 months. However, there was clinical evidence of recurring paraneoplastic endocrinopathy. Conclusion: For adult nephroblastoma, tumor stabilization and limited control of paracrine activity may be achieved by polychemotherapy.

Objective: It was the aim of this prospective randomized multicenter study to compare chemotherapy and radiotherapy as consolidation treatments in patients achieving complete remission (CR) after 6 cycles of doxorubicin-containing chemotherapy in advanced-stage Hodgkin's disease (HD).Methods: A total of 288 previously untreated patients aged 18-60 years with stage IIIB or IV HD received induction chemotherapy with 3 x (COPP + ABVD). Patients achieving CR were eligible for randomisation to either 20 Gy radiotherapy to initially involved fields (RT-arm) or to an additional 1 x (COPP + ABVD) (CT-arm). Patients with nodal PR were allocated to more intense radiotherapy (IRT-arm: 20 Gy IF,40 Gy to persisting tumor). Four patients with persisting organ involvement after induction received salvage chemotherapy.Results: Of 288 patients, 171 (59%) achieved CR after induction chemotherapy. Of these, 100 patients were successfully randomized to RT or CT. In the CT arm relapses were observed in 10 of 49 patients compared with 13 of 51 patients in the RT arm (p = n.s.). Fifty patients refused randomisation and for them a treatment was chosen, and 21 patients refused any further treatment. Of these 21 patients with no consolidation therapy, 9 relapsed, indicating an approximately 3-fold increased relapse risk compared with those receiving either of the consolidation therapies. No relapse was observed in initially involved lung or liver sites. Adverse prognostic factors for freedom from treatment failure and survival were low hemoglobin and large mediastinal mass at initial presentation.Conclusions: No statistically significant differences in treatment efficacy were detected between 20 Gy IF radiotherapy and 1 x (COPP + ABVD) chemotherapy following CR after six cycles of alternating chemotherapy in patients with advanced-stage HD. However, limited observations in a non-randomized cohort indicate that patients without consolidation treatment of CR after 6 cycles of chemotherapy may have an elevated risk for relapse.

Patients with advanced breast carcinoma should primarily be treated by endocrine modulation except those who are suffering from high-risk breast carcinoma, and response can be expected for more than half of the patients. Subsequently remissions can be obtained with second or third line hormonal treatment especially when the first line therapy was successful. Due to its efficacy and low toxicity, tamoxifen is still the endocrine therapy of first choice for postmenopausal patients. As second line hormonal therapy, high-dose gestagens or aminoglutethimide are equally effective. There may be some advantage in favor of the aromatase inhibitor as second line treatment, if third line data comparing aminoglutethimide with gestagens are taken into consideration. In the premenopausal patients, GnRH-agonists probably can replace oophorectomy or tamoxifen as first line therapy, followed by the sequence of tamoxifen, aromatase inhibitors and high-dose gestagens as recommended for the postmenopausal patient. Hormonal combination therapies using simultaneous or alternating schedules do not suggest additive response but in general show a high degree of toxicity. New hormonal drugs, e.g. aromatase inhibitors, promise more specific effects and reduced adverse reactions. Direct tumor-cytotoxic effects excerted by new antiestrogens or by GnRH-agonists and the development of antiprogestins may open new therapeutic perspectives.

In der Behandlung des fortgeschrittenen Mammakarzinoms steht, abgesehen von bestimmten Hochrisikosituationen, die hormonelle Therapie im Vordergrund. Nach einer hormonellen Erstbehandlung ist, insbesondere im Falle eines Ansprechens auf die primäre Hormon-therapie, eine zweite, ggf. auch eine dritte hormonelle Maßnahme durchaus noch erfolgversprechend. Nach allgemeinem Konsens gebührt in der postmenopausalen Situation dem Tamoxifen aufgrund seiner überlegenen Verträglichkeit der Platz der Erstbehandlung. Auch die Therapiesequenzdaten lassen zumindest eine Tendenz erkennen, die für das Tamoxifen als Erstmaßnahme spricht. In der weiteren Reihenfolge sind dann in der Zweittherapie Aminoglutethi-mid bzw. die Gestagene in etwa gleichwertig mit möglicherweise geringem Vorteil für den Aromatasehemmer. In der Prämenopause könnten die GnRH-Agonisten in Depotform die Ovarektomie als Erstmaßnahme auf die Dauer verdrängen, die weitere Reihenfolge der Substanzen könnte dann der Sequenz Tamoxifen-Aromatase-hemmer-Gestagen entsprechen. Die hormonelle Kombinationstherapie mit simultaner oder rasch alternierender Gabe der o.g. Einzelsubstanzen zeichnete sich bislang lediglich durch eine erhöhte Rate von Nebenwirkungen aus. Neue Substanzen mit spezifischerer Wirkungsweise, insbesondere der Aromatasehemmer, und besserer Steuerbarkeit mögen hier neue Aspekte bringen. Direkte zytotoxische Effekte durch neue Antiöstrogene und GnRH-Agonisten sowie die Verwendung von Antigestagenen eröffnen zusätzliche therapeutische Perspektiven.