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C Bokemeyer

Publications and source records attributed to C Bokemeyer.

At least 127 records · Page 7Linked to original sources
PubMed1999

Diagnosis and treatment of patients with testicular germ cell cancer.

Testicular germ cell tumours are a highly curable malignancy even in the presence of metastases, with an overall survival rate of approximately 90 to 95% when all stages are considered. Current therapeutic strategies aim at risk-adapted therapy, trying to maintain favourable overall results while reducing treatment-related toxicity, particularly in non-advanced disease. In stage I disease, unilateral inguinal orchiectomy represents the standard diagnostic and therapeutic approach. For patients with clinical stage I seminoma, prophylactic para-aortic radiotherapy with 26Gy is commonly employed. In patients with nonseminomatous germ cell tumours (NSGCT) at clinical stage I, the 3 options are: (i) retroperitoneal lymphadenectomy; (ii) a wait-and-see strategy; or (iii) 2 cycles of adjuvant chemotherapy. The individual risk profile for tumour recurrence, mainly based on histopathological criteria such as vascular tumour invasion, should guide treatment decisions in this group of patients. Radiotherapy is still the standard approach in clinical stage IIA/B seminoma, whereas in patients with a low tumour burden of NSGCT, retroperitoneal lymphadenectomy is frequently used followed by surveillance or adjuvant chemotherapy. Primary chemotherapy in these stages of disease may be at least equally successful. Major progress has also been achieved in the treatment of NSGCT patients with metastatic disease greater than clinical stage IIB, for whom primary chemotherapy represents the standard approach. After cisplatin-based combination chemotherapy, between 70 and 90% of patients will achieve a durable remission. In patients with 'good risk' metastatic disease, 3 cycles of cisplatin, etoposide and bleomycin (PEB) remain the standard treatment, despite several randomised trials trying to avoid the lung-toxic bleomycin or substituting cisplatin by carboplatin. In patients with 'intermediate' and 'poor prognosis' disease, 4 cycles of PEB given at 3-week intervals are considered routine treatment. The role of high dose chemotherapy with peripheral autologous blood stem cell transplantation is currently being investigated for patients presenting initially with advanced (poor prognosis) metastatic disease and for patients with relapse after previous chemotherapy, in whom conventional-dose salvage regimens will only result in 20% long-term survival. Because of the large group of patients with metastatic disease being cured, the possible long-term adverse effects of treatment have become important. Only a slightly elevated risk for therapy-related secondary malignancies has been identified. Long-term adverse effects associated with cisplatin may affect a larger proportion of patients. Further research should focus on reducing the risk of chemotherapy-related chronic toxicity.

Antineoplastic Agents↗
PubMed1999

UFT/calcium folinate plus weekly paclitaxel for solid tumors.

Since cancer is incurable in many patients, palliation of symptoms and quality-of-life issues are important aspects of therapy. Uracil and tegafur (UFT) plus calcium folinate are the components of the oral agent known as Orzel, which offers activity comparable to intravenously administered 5-fluorouracil (5-FU) combined with calcium folinate. Paclitaxel (Taxol), administered intravenously on a weekly schedule, offers high dose intensity and high response rates with limited hematologic toxicity. It is the aim of this phase I study to define the dose-limiting toxicity, possible antitumor activity, and appropriate phase II study dose for the combination of UFT plus calcium folinate administered orally for 4 weeks plus weekly doses of paclitaxel. The daily dose will be fixed at UFT 300 mg/m2 plus calcium folinate 90 mg, both divided into three doses per day; paclitaxel will be escalated in each cohort of patients in 10-mg/m2 steps, starting with 50 mg/m2 weekly. This protocol will take the success of protracted 5-FU infusion--here achieved orally with UFT plus calcium folinate--in combination with paclitaxel one step further by using paclitaxel in a dose-dense, less toxic weekly schedule. It may be anticipated that an active outpatient therapy for a variety of solid tumors will result.

Adolescent↗
PubMed1998

[Prognostic relevance of vena cava thrombosis in renal cell carcinoma].

The independent prognostic value of neoplastic extension of renal cell cancer (RCC) into the vena cava inferior has been the subject of several investigations reported to date. However, the use of vena cava thrombosis as an independent prognosticator of a patient's long-term survival is still debated. We have therefore correlated the clinical course of 53 patients with RCC and vena cava thrombosis with a control group consisting of 47 patients with renal cell tumors without vena cava thrombosis (follow-up: 1-154 months). The median long-term survival of patients with and without vena cava thrombosis was 32 and 35 months, respectively. Neither the propagation of the tumor into the vena cava (P = 0.391) nor the cranial extension of the thrombosis (P = 0.158)--even in case of propagation into the right atrium--could be identified as parameters of any prognostic value during univariate or multivariate statistical analysis.

Adult↗
PubMed1998

[Late toxicity after chemotherapy of malignant testicular tumors].

Improved survival in testicular cancer has been accompanied by concern about long-term side effects of chemotherapy or radiotherapy. Secondary malignant neoplasia represents one of the worst possible long-term complications, leading to death in patients cured of their primary malignancy. Patients with testicular germ cell tumors appear to have a 2-fold increased risk of developing any second cancer 25-30 years after the diagnosis, resulting in a cumulative incidence of 16-23% at that time. The risk for secondary solid tumors can be mainly attributed to radiotherapy. There is strong evidence of an increasing risk for secondary solid tumors with time since treatment. Tumor-specific analysis of the risk for second cancers revealed statistically significant excesses for stomach, pancreas, bladder, rectum, prostate, and kidney cancer, as well as for cancer of the thyroid, melanoma, sarcomas, and non-Hodgkin's lymphoma. No significantly elevated risk for secondary solid tumors was observed after treatment with chemotherapy alone. The risk of secondary leukemia was associated with both radiotherapy and in particular with chemotherapy. In recent clinical surveys of patients with testicular cancer, estimates of the risk of leukemia after chemotherapy have ranged from 10- to 300-fold. An elevated risk was observed within the first two decades after diagnosis, later the risk was as expected in the normal population. Etoposide seems to be leukemogenic, especially at cumulative doses higher than 2 g/m2, although the effects of dose and schedule as well as the effects of other cytotoxic agents and radiotherapy remain to be finally clarified. Based on currently available data in patients with testicular cancer, it can be concluded that a significant elevated risk for the development of secondary leukemia exits after chemotherapy. However this risk does by far not outweigh the therapeutic benefit of etoposid-based therapy in patients with germ cell tumors. Secondary Raynaud's phenomenon is the main late vascular toxicity affecting about one third of patients after curative chemotherapy for testicular cancer. Hypertension will occur in one fifths of the patients. The incidence of vascular toxicity appears to be lower following PEB-therapy compared to PVB-therapy and major vascular events seem to be rare. Other frequent symptomatic toxicities are ototoxicity and peripheral neuropathy. A major risk factor for the development of toxicity is the cumulative dose of cisplatin given. Alterations of gonadotropin levels and Leydig cell insufficiency persist in more than half of young patients cured from testicular cancer by cisplatin-based combination chemotherapy. Approximately one fourth of patients have low serum magnesium or phosphat levels, or elevated creatinine levels. These toxicities seldomly result in clinical symptoms. We conclude that 3-4 courses with bleomycin, cisplatin and etoposide in testicular cancer patients will only rarely lead to symptomatic impairment of organ functions and a decrease of quality of life. Germ cell cancers have served as a valuable model for the development of new treatment strategies contributing largely to defining the role of cisplatinum, etoposide and recently ifosfamide in medical oncology. However, germ cell cancer may also be a useful model for investigating the long term side effects of the oncological therapies. Thus, germ cell cancer is not only a "model for a curable neoplasm" (L.H. Einhorn) but can also be seen as a "model for the study of late sequelae of modern oncological therapies".

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Recent strategies for the use of paclitaxel in the treatment of urological malignancies.

Paclitaxel, a natural anticancer drug, has gained widespread acceptance as an active broad-spectrum antitumor agent, including its use in urological malignancies, particularly urothelial tract cancer and testicular cancer. The mechanism of action, based on the premature stabilization of the microtubule assembly with disruption of the cytoskeletal framework, is completely different from those of DNA-damaging agents, e.g., cisplatin and ifosfamide. As a single agent, paclitaxel is one of the most active drugs in metastatic bladder cancer, with an overall response rate of 40-50% being obtained in previously untreated patients. These promising single-agent results have prompted the use of combination regimens including, in particular, cisplatin and paclitaxel. A high degree of activity for the cisplatin-paclitaxel combination as reflected by responses in 50-80% of patients, including a substantial number of complete responses (> 30%), has been identified. The role of other agents such as vinorelbine, methotrexate, 5-fluorouracil, or ifosfamide as additions to this two-drug combination currently remains open. The combination of paclitaxel plus ifosfamide or vinorelbine in the absence of a platinum derivative has yielded rather disappointing results. Of particular interest may be the combination of paclitaxel and carboplatin. Both drugs can be given to patients with impaired renal function. Overall response rates of 45-60% have been reported in phase II studies. The so-called platelet-sparing effect of paclitaxel given in combination with carboplatin has resulted in a surprisingly low frequency of myelotoxicity, particularly thrombocytopenia. The combination of paclitaxel with carboplatin is being compared in an ongoing trial against the current standard MVAC regimen (methotrexate/vinblastine/Adriamycin/cisplatin) in patients with metastatic disease. Furthermore, the activity of paclitaxel-based combinations is currently being explored in the neoadjuvant setting in phase II studies, and the potential for the combination with the other new promising agent--gemcitabine--will be evaluated in a phase I setting. In prostate cancer, estramustine phosphate is widely used as palliative treatment for patients with hormone-refractory disease. In vitro synergistic activity has been observed between estramustine and paclitaxel in prostate-cancer cell lines, although paclitaxel has not demonstrated single-agent activity in patients with hormone-refractory prostate cancer. In clinical trials the combination of the two agents was associated with increased gastrointestinal toxicity. The addition of etoposide as a third drug has yielded prostate-specific antigen (PSA)-response rates of > 50%, but data on quality of life and survival time have not been reported for these combinations. A true clinical role for paclitaxel in prostate cancer has therefore not been established. Paclitaxel has finally demonstrated single-agent activity in relapsed and/or cisplatin-refractory testicular cancer in recent phase II trials, indicating different mechanisms of resistance to cisplatin and paclitaxel. These results have formed the rationale for the introduction of paclitaxel as part of combination chemotherapy regimens in patients with relapsed but chemosensitive testicular cancer. Preliminary results demonstrate that paclitaxel can be safely included into these conventional-dose combination regimens. When it is used prior to high-dose chemotherapy, sufficient numbers of peripheral blood stem cells (PBSCs) for high-dose therapy can be collected. The final role of paclitaxel in risk-adapted chemotherapeutic strategies in testicular cancer is not defined, but it appears that paclitaxel-based combinations can achieve a substantial response rate in patients with relapsed disease.

Antineoplastic Agents, Phytogenic↗
PubMed1998

Risk of secondary myeloid leukemia and myelodysplastic syndrome following standard-dose chemotherapy or high-dose chemotherapy with stem cell support in patients with potentially curable malignancies.

Secondary acute myeloid leukemia (s-AML) and secondary myelodysplastic syndrome (s-MDS) probably represent the worst possible long-term complications of cancer therapy in patients originally cured of their primary malignancy. The frequency and type of s-AML and s-MDS are reviewed for patients treated with standard and/or high-dose chemotherapy for Hodgkin's disease, non-Hodgkin's lymphoma (NHL), and breast or testicular cancer. Patients treated for Hodgkin's disease, have a 20- to 40-fold increased risk of developing s-AML, this risk increasing with the number of mechlorethamine-containing cycles given as well as following splenectomy and in patients more than 40-50 years of age. Generally, patients with NHL, breast or testicular cancer experience a lower, 2- to 15-fold, risk of developing s-AML. Epipodophyllotoxins appear to be the most important factor for s-AML in patients treated for testicular cancer. Doses of 2g/m2 or more are associated with an increased risk of s-AML and, with these high doses, a cumulative incidence of 2% 3% at 5 years is observed. Adjuvant cyclophosphomide, methobrexate, 5-Fu therapy in breast cancer patients does not appear to increase risk significantly as compared to the general population. The extent of the leukemogenic potential of anthracyclines remains to be defined. NHL patients receiving mechlorethamine, prednimustine or long-term maintenance therapy are also at an increased risk of s-AML. A considerably increased risk of developing AML, with a cumulative incidence of approximately 9% at 5 years, has been observed following allogenic bone marrow transplantation (ABMT) or peripheral stem cell transplantation (PBSCT) in patients with NHL. It is likely that the increased risk of s-AML/s-MDS following high-dose chemotherapy with ABMT or PBSCT is related to prior treatment rather than to high-dose chemotherapy itself. However, this issue remains to be conclusively addressed. s-AML or s-MDS rarely develops after allogenic bone marrow transplantation. s-AML and s-MDS increasingly represent a problem in modern cancer therapy because of better treatment strategies, which result in improved cure rates. Patients who receive chemotherapy must be informed about the potential risk of developing s-AML or s-MDS. Future studies should include a follow-up long enough to record the occurrence of all s-AML/s-MDS and all potential influencing factors reliably. These data would enable risk factors to be defined and risk/benefit analyses to be carried out, allowing the correct assessment of current and future therapy strategies.

Acute Disease↗
PubMed1998

Phase I pharmacological study of intra-arterially infused fotemustine for colorectal liver metastases.

Fotemustine was investigated in 17 patients with progressive hepatic metastases from colorectal carcinoma to define the maximally tolerated dose for a daily hepatic intra-arterial infusion (HAI) schedule. Haematotoxicity was delayed, dose-dependent and related to pretreatment, with thrombo- and leucocytopenia being dose-limiting. Local side-effects at the liver were mild. Infection (WHO grade III) occurred in 1 patient due to neutropenia. Other side-effects, particularly renal, pulmonal, neurological or cardiac toxicity, mucositis and diarrhoea, hair loss or allergic reactions did not occur. Pharmacokinetic analysis indicated a short plasma half-life (t1/2 = 25.8 +/- 11.5 min) and a high body clearance (CL = 2193 +/- 870 ml/min) with large inter- and intra-individual variations. Of 15 evaluable patients, one complete and three partial responses were observed (ORR = 27%; CI95% [4.5-49.5%]). All tumour remissions appeared at higher dose levels in previously untreated patients. Considering the absence of mucosal side-effects, such as mucositis/diarrhoea and of hepatic toxicity, this agent was well tolerated. The recommended intra-arterial dose for consecutive phase II trials is 125 mg/m2/day1-3.

Adolescent↗
PubMed1998

The prognostic value of p53 for long-term and recurrence-free survival following radical prostatectomy.

In the present study, 76 specimens (T1-T4) from 76 randomly selected patients undergoing radical prostatectomy at Hannover University as well as in the Josef Hospital Regensburg (13 patients) between 1980 and 1992 for whom tissue sections for immunohistochemical investigation were available, were investigated for different biological and clinical characteristics as predictors for long-term and recurrence-free survival: age, depth of tumour infiltration, histological grade, lymph node status, as well as overexpression of the p53 protein (monoclonal antibody DO-1). After a median follow-up of 50 months, 6 of 18 patients (33%) with more than 20% of tumour cells stained positively for p53 died from tumour progression compared with 9 of 58 patients (16%) with less than 20% of tumour cells positive for p53. During univariate analysis, p53 overexpression (P = 0.011), histological grading (P = 0.009) and tumour stage (P = 0.024) were significant prognostic factors for survival, among which only p53 overexpression (P = 0.026) remained an independent significant predictor in multivariate analysis. Additionally, 18 of 66 patients (27%) with less than 40% positivity for p53 suffered tumour recurrence in contrast to 6 of 10 patients (60%) with more than 40% tumour cells exhibiting a positive staining reaction. In multivariate analysis, p53 overexpression was identified as the only prognostic parameter for recurrence-free survival (P = 0.005). Prospective studies are needed to confirm the independent prognostic potential of p53 overexpression in patients with localised prostate cancer. The availability of more refined prognostic factors should assist decision making regarding the value of radical prostatectomy versus a surveillance strategy for prognostically defined subgroups of patients.

Aged↗
PubMed1998

Analysis of risk factors for cisplatin-induced ototoxicity in patients with testicular cancer.

This study evaluates the degree and relevance of persisting ototoxicity after cisplatin-based standard-dose chemotherapy for testicular cancer, with emphasis on identification of potential factors for an increased risk of this late sequel. Hearing thresholds of 86 patients with a median age of 31 years (range 21-53 years) and a median follow-up time of 58 months (range 15-159 months) were assessed by conventional pure-tone audiometry. Interviews were conducted evaluating the patients' history with special regard to audiological risk factors, as well as circumstances of ototoxic symptoms. Details concerning treatment and patient variables were extracted retrospectively from the patients' charts. An additional screening programme assessed current body functions, blood parameters and other late toxicities. Symptomatic ototoxicity persisted in 20% of patients (59% tinnitus, 18% hearing loss, 23% both), while 10% had experienced completely reversible ototoxic symptoms for a duration of 1-18 months after treatment. Symptoms were bilateral in 81% of patients. Hearing thresholds were compatible with cisplatin-induced hearing loss in 42% of audiograms performed. Subjective (history) and objective (audiogram) findings were not always consistent. The following statistically significant risk factors for ototoxicity were established: high cumulative dose of cisplatin (P < 0.0001); history of noise exposure (P = 0.006). Additionally, high doses of vincristine (P = 0.001) seemed to result in reversible ototoxic symptoms. No other independent risk factors were identified. In conclusion, persisting ototoxicity represents a clinical sequel for approximately 20% of testicular cancer patients treated at standard dose but may affect more than 50% of patients receiving cumulative doses of cisplatin > 400 mg m(-2). Previous noise exposure may also result in a threefold increased risk for cisplatin ototoxicity. Future studies should use these risk factors as important stratification criteria for trials aiming at the evaluation and prevention of cisplatin-induced ototoxicity.

Adult↗
PubMed1998

Expression of E-cadherin in primary prostate cancer: correlation with clinical features.

OBJECTIVE: To correlate the immunohistochemically detected loss of E-cadherin expression with patient age, clinical and biological variables, and to investigate the prognostic value of these variables for the relapse-free and overall survival of patients with different stages of newly diagnosed prostate cancer. PATIENTS AND METHODS: Sixty-seven patients (median age 63 years, range 48-78) undergoing radical prostatectomy for the treatment of primary prostate cancer were assessed to determine whether age, tumour stage, histological grading, serum levels of prostate specific antigen and prostatic acid phosphatase, regional lymph node status and E-cadherin expression were prognostic factors for relapse-free and overall survival. RESULTS: With a median (range) follow-up of 54 (3-193) months, there was no independent prognostic value of decreased E-cadherin expression for the long-term or recurrence-free survival of patients, using a threshold value of 40% for the relative amount of positively stained tumour cells, or for any other threshold value calculated (25%, 60% or 75%). However, comparing a follow-up of 16 months in patients with < 40% positivity and 46 months in patients with > or = 34% positivity, those patients retaining E-cadherin expression had a significantly longer recurrence-free interval after radical prostatectomy (P < 0.01). CONCLUSION: The value of E-cadherin expression as an additional independent prognostic variable for patients with primary prostate cancer is questionable.

Adenocarcinoma↗
PubMed1998

Phase II study of continuous 120 h infusion of mitomycin C as salvage chemotherapy in patients with progressive or rapidly recurrent colorectal cancer.

We evaluated the therapeutic activity and safety of continuously infused mitomycin C in patients with metastatic colorectal cancer who had recurred (less than 3 months) or progressed following first- or second-line 5-fluorouracil-based chemotherapy. Treatment consisted of mitomycin C 20 mg/m2 i.v. given over 120 h (5 days) followed by a 3 week rest period. Fifty-two consecutively enrolled patients were assessable for toxicity and 49 for response evaluation (three patients evaluable but not measurable), completing at least one full course of chemotherapy. Previous chemotherapy regimens consisted of bolus 5-fluorouracil/folinic acid (5-FU/FA) (Machover) n=26 (50%) or continuous (24 h) 5-FU+/-FA+/-interferon n=26 (50%). Forty-two percent of patients had received one previous chemotherapy regimen and 58% more than one. One partial remission (2%) lasting 7 months and 11 disease stabilizations (23%) with a median duration of 3.2 months (range 1-8) were achieved in 49 patients. Median survival time since start of mitomycin C was 4.7 months (1.2-28.1) resulting in a 6 month survival rate of 36%. The progression-free interval was 10 weeks (range 4-36). Delayed and cumulative thrombo- and leukocytopenia (WHO grade III/IV) were observed in 19 and 6%, and anemia in 2% of patients. WHO grade I/IV mucositis, diarrhea and fever/infection occurred each in 6% of patients. Treatment delays and dose reductions were necessary in 11 (21%) and 21 (40%) patients, respectively. In three cases treatment was stopped due to cumulative thrombocytopenia (6%). Continuous infusion of single-agent mitomycin C displays modest activity in heavily pretreated 5-FU refractory colorectal cancer patients combined with a low toxicity level.

Adult↗
PubMed1998

Secondary leukemia following high cumulative doses of etoposide in patients treated for advanced germ cell tumors.

PURPOSE: High cumulative epipodophyllotoxin dosages are reported to be associated with an elevated risk for secondary acute myeloid leukemia (s-AML). This study examined the risk of s-AML following cumulative etoposide doses greater than 2 g/m2 in patients with metastatic germ cell tumors (GCT). PATIENTS AND METHODS: The incidence of s-AML was retrospectively assessed in patients treated within clinical trials between January 1986 and February 1996 at four university centers. All patients received high-dose chemotherapy (HDCT) plus autologous stem-cell support for metastatic GCT, including high cumulative etoposide doses (> 2 g/m2). Minimum patient follow-up was 12 months. Standardized morbidity ratio (SMR) was calculated to estimate the risk associated with high cumulative etoposide doses, as compared with the general population. RESULTS: A total of 302 patients with a median age of 29 years (range, 15 to 55) received a median cumulative etoposide dose of 5 g/m2 (range, 2.4 to 14 g/m2). Four cases of s-AML were observed, which resulted in a cumulative incidence of 1.3% (95% confidence interval [CI], 0.38% to 3.59%) at 52 months of median follow-up (range, 12 to 198). Two cases of secondary myelodysplasia (s-MDS) developed in patients with primary mediastinal GCT. Based on the observed four cases of AML, which are most likely etoposide-related, the risk for developing s-AML (SMR, 160 [95% CI, 43.7 to 411.2]) is significantly increased in comparison to the age-matched general population. CONCLUSION: Due to the low incidence of AML in the general population, the significantly elevated risk for developing s-AML affects only 1.3% of all patients who receive etoposide doses greater than 2 g/m2. HDCT, including etoposide doses greater than 2 g/m2, is associated with an acceptably low incidence of s-AML in patients with advanced GCT.

Acute Disease↗
PubMed1998

The use of dose-intensified chemotherapy in the treatment of metastatic nonseminomatous testicular germ cell tumors. German Testicular Cancer Study Group.

With the use of a cisplatin-based chemotherapy, metastatic testicular cancer has become a model for a highly curable malignant disease. Current data show that 70% to 80% of patients with this disease will achieve long-term survival following cisplatin/etoposide/bleomycin therapy. The role of high-dose chemotherapy with autologous stem cell support is being investigated in metastatic germ cell cancer in attempts to improve outcome for patients whose disease relapses after standard-dose chemotherapy and for those who present initially with advanced metastatic disease. Prognostic categories for patients receiving high-dose salvage chemotherapy have recently been developed: cisplatin-refractory disease, beta-human chorionic gonadotropin values greater than 1,000 U/L, and primary mediastinal germ cell tumors are factors characterizing patients who will derive less benefit from high-dose chemotherapy than those with chemosensitive disease at relapse. While standard-dose salvage chemotherapy achieves only a 20% long-term survival rate, high-dose salvage chemotherapy may yield a cure rate of approximately 40%. A randomized study comparing high-dose therapy with conventional-dose therapy (IT94 coordinated by the European Group for Blood and Marrow Transplantation) in patients with relapsed disease is ongoing to substantiate this observation. The use of dose-intensive therapy as first-line treatment is currently being studied by several institutions. High-dose therapy may be better tolerated when used first line compared with its use in the salvage situation, and may also achieve a rapid initial cell kill before cytostatic drug resistance develops. The German Testicular Cancer Study Group has developed a sequential high-dose combination regimen of cisplatin/etoposide/ifosfamide given with granulocyte colony-stimulating factor and peripheral blood stem cell support for four cycles every 3 weeks. This ongoing study, started in 1990, had accrued 218 patients with advanced testicular germ cell tumors as of June 1997. Of 141 evaluable patients receiving dose levels 1 through 5, 82 (58%) have achieved complete remission with no evidence of disease and 32 (23%) have achieved partial remission with marker normalization. The early death rate was 8%. Overall and event-free survival rates at 2 years are 78% and 73%, respectively, with a projected 5-year overall survival rate of 74%. Despite favorable preliminary results, this approach cannot be considered standard treatment. Currently, high-dose chemotherapy with peripheral blood stem cell transplantation should be administered to patients with testicular cancer only within controlled clinical trials to allow long-term cure rates and treatment-related late side effects to be evaluated.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

A phase I/II study of sequential, dose-escalated, high dose ifosfamide plus doxorubicin with peripheral blood stem cell support for the treatment of patients with advanced soft tissue sarcomas.

BACKGROUND: This Phase I/II study investigates increasingly high doses of ifosfamide combined with full dose doxorubicin chemotherapy supported with peripheral blood stem cells (PBSC) and granulocyte-colony stimulating factor (G-CSF) in patients with metastatic soft tissue sarcoma (STS). METHODS: Patients with histologically proven metastatic or advanced adult STS without prior treatment received doxorubicin, 75 mg/m2, on Day 1 followed by 4-day continuous infusion of ifosfamide at 5 consecutive dose levels starting with 8 g/m2 and escalating to 16 g/m2 in increments of 2 g/m2. Three patients per dose level and a maximum of 5 treatment cycles per level at 3-week intervals were planned. Each cycle was followed by G-CSF and retransfusion of PBSC. PBSC separation was performed prior to chemotherapy by steady state mobilization with G-CSF. RESULTS: Eighteen patients (median age, 45 years, range, 25-57 years) were included, with 4, 3, 4, 4, and 3 patients assigned to Levels 1-5, respectively. Metastatic sites included the lungs in 12 patients (67%), lymph nodes in 8 patients (44%), and the liver in 5 patients (28%). Nine patients (50%) achieved objective responses with 4 complete responses (22%) and 5 partial responses (28%). Lung metastases and a histology of synovial sarcoma or malignant fibrous histiocytoma were favorable features for response to therapy. The median survival for all patients was 13+ months (range, 3-19+ months). Hematotoxicity was manageable and treatment could be administered at a median interval of 24 days. One case of World Health Organization Grade 3 neurotoxicity occurred. Nephrotoxicity was dose-limiting, with 1 patient in Level 4 (WHO Grade 2) and 2 patients in Level 5 (WHO Grade 3). CONCLUSIONS: Multiple cycles of dose-intensive therapy with doxorubicin and high dose ifosfamide can be administered safely with PBSC support. Nephrotoxicity is dose-limiting for ifosfamide at total doses of 16 g/m2. Multiple cycles of high dose chemotherapy at short treatment intervals using ifosfamide at a dose of 14 g/m2 should be investigated further in a neoadjuvant setting in patients with STS.

Adult↗
PubMed1997

[Current aspects of adjuvant and palliative chemotherapy in colorectal carcinoma].

With an annual incidence rate of 30 to 40 per 100,000 colorectal carcinoma is the second most frequent malignancy in Germany. Despite the poor outcome of patients suffering from this disease important advances have been made in the standardisation and improvement of palliative and adjuvant treatment in patients with colorectal cancer. For the systemic chemotherapy 5-fluorouracil (5-FU) remains the most important cytotoxic agent and biomodulation of the therapeutic activity of 5-FU with methotrexate or particularly folinic acid has been clinically established, yielding response rates in 20 to 35% of patients. Current investigations of systemic treatment are aiming into three directions: 1. investigation of high-dose continuous (24-hours) 5-FU application (with or without modulation by folinic acid); 2. evaluation of new, effective cytotoxic agents, among which the camphotecin derivative CPT-11 (irenotecan) and the specific thymidilate synthase inhibitor Tomudex appear to be the most promising drugs as single agents and/or in combination with 5-FU; 3. use of orally available fluoropyrimidine derivatives with high bioavailability which may substantially improve the quality of life in palliative therapy. The postoperative adjuvant treatment of patients with Dukes C colorectal cancer is established clinical practice and the combination of 5-FU and levamisol given for one year will result in an improved overall survival of about 15% at five years compared to surgery alone. Although this regimen remains the current standard treatment, alternatives for the adjuvant treatment may be the use of 5-FU and folinic acid given for only half a year post surgery, locoregional perfusion of the liver with 5-FU alone via the portal vene by 7-day continuous application or the use of 17-1A monoclonal antibody immunotherapy after curative resection. Further improvement may be achieved by the combination of immunotherapy and chemotherapy which is currently tested in clinical studies. Future recommendations for the adjuvant treatment of colorectal cancer will not only be based on therapeutic efficacy but will also have to take costs of treatment into account. Better definition of high-risk patient groups for adjuvant treatment is needed.

Antineoplastic Agents↗
PubMed1997

[The synchronous occurrence of acute myeloid leukemia and kidney carcinoma].

HISTORY AND CLINICAL FINDINGS: During the past year a 52-year-old man had developed quarterly bouts of fever, up to 38.5 degrees C, associated with fatigue and arthralgia. The fourth bout continued as undulating periods of fever with markedly impaired general state. Physical examination was unremarkable except for mild generalised lymphadenopathy. INVESTIGATIONS: Extensive imaging and serological studies failed to find an infectious or autoimmunological cause. But computed tomography and angiography revealed a space-occupying lesion in the left kidney, yet the suspected diagnosis of renal carcinoma insufficiently explained the clinical picture. DIAGNOSIS TREATMENT AND COURSE: Haematological tests having shown anaemia (Hb 8.1 g/dl) and blast cells (10%) in the peripheral blood a bone marrow biopsy was performed which indicated acute myeloid leukaemia. Three courses of intensive chemotherapy brought about only partial remission and the patient died 6 months later from a cerebral haemorrhage. An autopsy confirmed both the acute myeloid leukaemia and a renal carcinoma. CONCLUSION: The possibility of synchronous occurrence of two malignancies should always be kept in mind especially if the initially diagnosed tumor cannot explain the clinical symptoms.

Acute Disease↗
PubMed1997

[An interdisciplinary consensus conference on the diagnosis and therapy of testicular tumors].

In 1988 the German testicular working group was set up by leading experts in the fields of urology, medical and radio-oncology. Since then, the working group has initiated several clinical studies and conferences with the aim of defining current standards in the treatment of testicular germ cell tumours. After a series of preliminary joint meetings with representatives from the AUO, AIO and ARO of the "Deutsche Krebsgesellschaft", a conference was held in May 1996 to agree on a consensus in diagnosis and treatment of testicular germ cell tumours. The standards which have been agreed on at the conference refer to the current international literature and provide recommendations for the majority of clinical situations. Treatment strategies differing from these standards should not be chosen except for well argued individual settings or patients treated in clinical trials. No consensus could be reached for nonseminomatous stage I, IIA and IIB tumours. As a consequence, the differing treatment strategies for these stages are summarized in this paper. A subsequent conference in later years is needed to possibly find an agreement for these tumour stages and to update the current standards according to new clinical experience and knowledge.

Combined Modality Therapy↗