[Guideline 'Renal cell carcinoma']. / Richtlijn 'Niercelcarcinoom'.

Each year, more than 1500 new cases of renal cell carcinoma are diagnosed in the Netherlands, and approximately 850 patients die due to this disease. The guideline 'Renal cell carcinoma' contains clinical practice recommendations on the diagnosis (imaging, pathological assessment, histopathological classification) and treatment (surgery, chemo-, immuno-, and radiotherapy) of renal cell carcinoma. For diagnostic imaging, chest and abdominal CT is recommended. Scintigraphy is not recommended. The term 'Grawitz tumour' is obsolete and should be replaced by 'renal cell carcinoma' with histological subtype specification according to the 2004 WHO classification. Laparoscopic radical nephrectomy is as effective as open surgery for localised tumours (T1 and T2) and possibly also for T3 tumours. The laparoscopic approach is associated with less morbidity due to the less invasive nature of this technique. This operation requires experience. In partial nephrectomy, a small margin of healthy tissue is sufficient. Frozen section examination of the resection edges does not appear to be required. In patients with metastatic renal cell carcinoma who are eligible for immunotherapy, removal of the tumour prolongs survival. Metastasectomy prolongs survival in patients with a solitary metastasis. Most currently available cytotoxic agents are ineffective against renal cell carcinoma. Interferon-alpha may have a role in the treatment of patients with renal cell carcinoma and favourable prognostic factors, given the survival advantage demonstrated with this agent in clinical trials. The guideline is available in English at www.oncoline.nl.

[Angiogenesis inhibitors for the systemic treatment of metastatic renal cell carcinoma: sunitinib, sorafenib, bevacizumab and temsirolimus]. / Angiogeneseremmers voor de systemische behandeling van gemetastaseerd niercelcarcinoom: sunitinib, sorafenib, bevacizumab en temsirolimus.

Treatment of patients with metastatic renal cell carcinoma is evolving rapidly due to the advent of novel targeted therapies. Improved knowledge of the underlying pathogenesis has led to the development of drugs that modulate the dominant signal transduction pathways for this disease, which results in inhibition of angiogenesis. Recent evidence indicates that the receptor tyrosine kinase inhibitor sunitinib prolongs progression-free survival compared with interferon-alpha, especially in patients with intermediate risk. Immunotherapy with interferon-alpha or high-dose interleukin-2 should still be considered for low-risk patients, particularly those with clear-cell tumours and metastases of the lung only. In patients who fail treatment with interferon-alpha, sorafenib has been shown to improve progression-free survival. High-risk patients may benefit from treatment with temsirolimus, which inhibits mammalian target of rapamycin (mTOR) kinase activity and has shown to improve overall survival. These angiogenesis inhibitors did not receive mention in the recently published guideline 'Renal cell carcinoma'.

Dynamics in chimerism of T cells and dendritic cells in relapsed CML patients and the influence on the induction of alloreactivity following donor lymphocyte infusion.

Donor lymphocyte infusion (DLI) after allogeneic SCT induces complete remissions in approximately 80% of patients with relapsed CML in chronic phase, but some patients do not respond to DLI. We studied absolute numbers of dendritic cell (DC) subsets and chimerism in T cells and two subsets of blood DCs (myeloid DCs (MDCs) and plasmacytoid DCs (PDCs)) in relation to DLI-induced alloreactivity. Based on T cell and DC chimerism, we identified three groups. Four patients were completely donor chimeric in T cells and DC subsets. These patients had an early stage of relapse, and three of the four patients attained complete molecular remission (CMolR) without significant GVHD. Six patients were completely donor in T cells and mixed chimeric in DC subsets. All patients entered CMolR, but this was associated with GVHD in four and cytopenia in three patients. Five patients had mixed chimerism in T cells and complete recipient chimerism in MDC; only two patients entered CMolR. Our data suggest that the combination of donor T cells and mixed chimerism in DC subsets induces a potent graft-versus-leukemia (GVL) effect in association with GVHD. DLI in patients with an early relapse and donor chimerism in both T cells and DC subsets results in GVL reactivity without GVHD.

Impact of the treating institution on survival of patients with "poor-prognosis" metastatic nonseminoma. European Organization for Research and Treatment of Cancer Genito-Urinary Tract Cancer Collaborative Group and the Medical Research Council Testicular Cancer Working Party.

BACKGROUND: Because metastatic nonseminomatous germ cell cancer is a rare but treatable cancer, we have explored whether there is an association between the experience of the treating institution with this disease and the long-term clinical outcome of the patients, particularly patients with a poor prognosis. METHODS: We analyzed data on 380 patients treated in one of 49 institutions participating in the European Organization for Research and Treatment of Cancer/ Medical Research Council randomized trial of four cycles of bleomycin-etoposide-cisplatin followed by two cycles of etoposide-cisplatin versus three cycles of bleomycin-vincristine-cisplatin followed by three cycles of etoposide-ifosfamide-cisplatin-bleomycin, both treatment regimens given with or without filgrastim (granulocyte colony-stimulating factor). Institutions were divided into four groups based on the total number of patients entered in the trial. The groups were compared by use of the Cox proportional hazards model stratified for treatment with filgrastim and for patient prognosis as defined by the International Germ Cell Consensus Classification Group. With the use of this classification, only 65 % of the patients had a poor prognosis. RESULTS: Patients treated in the 26 institutions that entered fewer than five patients into the trial had an overall survival that was statistically significantly worse (two-sided P = .010; hazard ratio = 1.85; 95% confidence interval = 1.16-3.03) than that of patients treated in the 23 institutions that entered five patients or more. Overall survival and failure-free survival were similar among institutions that entered at least five patients. The observed effect may be related to differences in adherence to the chemotherapy protocol and in the frequency and extent of surgery for residual masses, although only the differences in dose intensity achieved statistical significance. CONCLUSIONS: Patients treated in institutions that entered fewer than five patients into the trial appeared to have poorer survival than those treated in institutions that entered a larger number of patients with "poor-prognosis" nonseminoma.

Randomized phase III trial of edatrexate versus methotrexate in patients with metastatic and/or recurrent squamous cell carcinoma of the head and neck: a European Organization for Research and Treatment of Cancer Head and Neck Cancer Cooperative Group study.

PURPOSE: To compared the response rates and the toxicity of the new antifolate edatrexate (EDX) with that of methotrexate (MTX) in a randomized trial in patients with metastatic or recurrent squamous cell cancer of the head and neck (SCC) and to compare the durations of response and survival. PATIENTS AND METHODS: Two hundred seventy-three patients with SCC were randomized to receive either EDX or MTX as a weekly intravenous (IV) bolus injection. Doses of EDX were initially 80 mg/m2/wk, but because of the toxicity, this was later reduced to 70 mg/m2/wk. MTX was administered at a dose of 40 mg/m2/wk throughout. In both arms, two dose increments of 10% were scheduled in case of no toxicity. RESULTS: Of 264 eligible patients, 131 were treated with EDX and 133 with MTX. There were five treatment-related deaths: four on EDX and one on MTX. Overall, toxicity was similar in both arms; however, stomatitis, skin toxicity, and hair loss were more pronounced on the EDX arm. The overall response rate was 21% (six complete responses [CRs] and 21 partial responses [PRs]) for EDX and 16% (nine CRs and 12 PRs) for MTX (P = .392). Responses were mainly seen in patients with locoregional disease. Tumors that originated from the hypopharynx responded poorly in comparison to tumors from other sites. The median duration of response was 6.1 months for EDX and 6.4 months for MTX (log-rank P = .262). There was no difference in overall or progression-free survival. The median survival duration was 6 months on both treatment groups. CONCLUSIONS: Both EDX and MTX are moderately active against SCC. In this large phase III study, response rates, time to treatment failure, and overall survival appeared to be similar for both antifolates. However, EDX had more side effects than MTX and therefore cannot be recommended for routine palliative treatment of patients with SCC.

Analysis of cumulative probabilities shows that the efficacy of 5HT3 antagonist prophylaxis is not maintained.

PURPOSE: Several investigators have reported that the efficacy of 5HT3 receptor antagonists is maintained over repeated cycles of chemotherapy. These investigators presented conditional probabilities of protection. Because conditional analyses by definition only include patients with protection in previous cycles, the results are flattered. PATIENTS AND METHODS: We applied a novel statistical approach to investigate whether the efficacy of the 5HT3 receptor antagonist ICS 205-930 (tropisetron) is maintained over repeated cycles of weekly high-dose cisplatin. Overall protection was determined based on cumulative probabilities with the Kaplan-Meier method. Complete protection was calculated with a three state model for transitional probabilities. Eighty-three patients were studied. RESULTS: Over six consecutive cycles, protection against both acute and delayed emesis decreased significantly. The initial complete and overall protection rates against acute emesis of 71% and 95%, respectively, decreased to 43% and 72% in the sixth cycle of chemotherapy. Similarly, the protection rates of 31% and 68% against delayed emesis decreased to 6% and 40%, respectively. CONCLUSION: We conclude that overall and complete long-term protection is more accurately measured by cumulative probabilities than with a method that is based on conditional probabilities. Our statistical approach shows that the efficacy of 5HT3 antagonists is not maintained.

Equivalence of three or four cycles of bleomycin, etoposide, and cisplatin chemotherapy and of a 3- or 5-day schedule in good-prognosis germ cell cancer: a randomized study of the European Organization for Research and Treatment of Cancer Genitourinary Tract Cancer Cooperative Group and the Medical Research Council.

PURPOSE: To test the equivalence of three versus four cycles of bleomycin, etoposide, and cisplatin (BEP) and of the 5-day schedule versus 3 days per cycle in good-prognosis germ cell cancer. PATIENTS AND METHODS: The study was designed as a 2 x 2 factorial trial. The aim was to rule out a 5% decrease in the 2-year progression-free survival (PFS) rate. The study included the assessment of patient quality of life. A cycle of BEP consisted of etoposide 500 mg/m(2), administered at either 100 mg/m(2) days 1 through 5 or 165 mg/m(2) days 1 through 3, cisplatin 100 mg/m(2), administered at either 20 mg/m(2) days 1 through 5 or 50 mg/m(2) days 1 and 2. Bleomycin 30 mg was administered on days 1, 8, and 15 during cycles 1 through 3. The randomization procedure allowed some investigators to participate only in the comparison of three versus four cycles. RESULTS: From March 1995 until April 1998, 812 patients were randomly assigned to receive three or four cycles: of these, 681 were also randomly assigned to the 5-day or the 3-day schedule. Histology, marker values, and disease extent are well balanced in the treatment arms of the two comparisons. The projected 2-year PFS is 90.4% on three cycles and 89.4% on four cycles. The difference in PFS between three and four cycles is -1.0% (80% confidence limit [CL], -3.8%, +1.8%). Equivalence for three versus four cycles is claimed because both the upper and lower bounds of the 80% CL are less than 5%. In the 5- versus 3-day comparison, the projected 2-year PFS is 88.8% and 89.7%, respectively (difference, -0.9%, (80% CL, -4.1%, +2.2%). Hence, equivalence is claimed in this comparison also. Frequencies of hematologic and nonhematologic toxicities were essentially similar. Quality of life was maintained better in patients receiving three cycles; no differences were detected between 3 and 5 days of treatment. CONCLUSION: We conclude that three cycles of BEP, with etoposide at 500 mg/m(2), is sufficient therapy in good-prognosis germ cell cancer and that the administration of the chemotherapy in 3 days has no detrimental effect on the effectiveness of the BEP regimen.

Filgrastim during combination chemotherapy of patients with poor-prognosis metastatic germ cell malignancy. European Organization for Research and Treatment of Cancer, Genito-Urinary Group, and the Medical Research Council Testicular Cancer Working Party, Cambridge, United Kingdom.

PURPOSE: To determine the effect of r-metHu granulocyte colony-stimulating factor (G-CSF) on the proportion of patients with metastatic poor-prognosis malignant germ cell tumors who receive full dose-intensity combination chemotherapy. PATIENTS AND METHODS: In a phase III study patients received six cycles of BEP/EP (etoposide, and cisplatin, plus or minus bleomycin) or six cycles of BOP/VIP-B (bleomycin, vincristine, cisplatin/etoposide, ifosfamide, cisplatin, bleomycin). A subset were secondarily randomized to receive or not receive filgrastim. Filgrastim 5 microg/kg/day was administered subcutaneously on days 3 through 9 after each BOP and on days 6 through 19 after each VIP, BEP, or EP cycle. RESULTS: Eighty-five percent of 120 eligible patients randomized to filgrastim received at least six chemotherapy cycles compared with 70% of 130 patients randomized to not receive filgrastim (VCP = .003). Patients in the filgrastim-arm achieved significantly higher dose-intensities. Neutropenic fever occurred in 25 of 128 filgrastim-patients and in 38 of 129 non-filgrastim-patients (P = .052). Twelve and three toxic deaths occurred in the non-filgrastim- and filgrastim-arms, respectively. Nine of the 12 toxic deaths and all of the three toxic deaths were associated with febrile grade 4 neutropenia. Failure-free and overall survival were similar in both arms. CONCLUSION: During combination chemotherapy in patients with malignant germ cell tumors, the routine use of filgrastim significantly improved the delivery of the planned treatment schedule without effect on failure-free or overall survival. The use of filgrastim was associated with a clinically important reduction in the number of toxic deaths, confined to the experimental intensified-chemotherapy schedule. This study does not support the routine use of filgrastim during standard chemotherapy with BEP.

Randomized phase III trial of high-dose-intensity methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) chemotherapy and recombinant human granulocyte colony-stimulating factor versus classic MVAC in advanced urothelial tract tumors: European Organization for Research and Treatment of Cancer Protocol no. 30924.

PURPOSE: This randomized trial evaluated antitumor activity of and survival asociated with high-dose-intensity chemotherapy with methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) plus granulocyte colony-stimulating factor (HD-MVAC) versus MVAC in patients with advanced transitional-cell carcinoma (TCC). PATIENTS AND METHODS: A total of 263 patients with metastatic or advanced TCC who had no prior chemotherapy were randomized to HD-MVAC (2-week cycles) or MVAC (4-week cycles). RESULTS: Using an intent-to-treat analysis, at a median follow-up of 38 months, on the HD-MVAC arm there were 28 complete responses (CRs) (21%) and 55 partial responses (PRs) (41%), for an overall response of 62% (95% confidence interval [CI], 54% to 70%). On the MVAC arm, there were 12 CRs (9%) and 53 PRs (41%), for an overall response of 50% (95% CI, 42% to 59%). The P value for the difference in CR rate was.009; and for the overall response, it was.06. There was no statistically significant difference in survival (P =.122) or time to progression (P =.114). Progression-free survival was significantly better with HD-MVAC (P=.037; hazard ratio.75; 95% CI.58 to.98). The median progression-free survival time was 9.1 months on the HD-MVAC arm versus 8.2 months on the MVAC arm. The 2-year progression-free survival rate was 24.7% for HD-MVAC (95% CI, 17.1% to 32.3%) versus 11.6% for MVAC (95% CI, 5.9% to 17.4%). CONCLUSION: With HD-MVAC, it was possible to deliver twice the doses of cisplatin and doxorubicin in half the time, with fewer dose delays and less toxicity. Although a 50% difference in median overall survival was not detected, a benefit was observed in progression-free survival, CR rates, and overall response rates with HD-MVAC.

Randomized trial of bleomycin, etoposide, and cisplatin compared with bleomycin, etoposide, and carboplatin in good-prognosis metastatic nonseminomatous germ cell cancer: a Multiinstitutional Medical Research Council/European Organization for Research and Treatment of Cancer Trial.

PURPOSE: This prospective randomized multicenter trial was designed to evaluate the efficacy of carboplatin plus etoposide and bleomycin (CEB) versus cisplatin plus etoposide and bleomycin (BEP) in first-line chemotherapy of patients with good-risk nonseminomatous germ cell tumors. PATIENTS AND METHODS: Between September 1989 and May 1993, a total of 598 patients with good-risk nonseminomatous germ cell tumors were randomized to receive four cycles of either BEP or CEB. In each cycle, the etoposide dose was 120 mg/m2 on days 1, 2, and 3, and the bleomycin dose was 30 U on day 2. BEP patients received cisplatin at 20 mg/m2/d on days 1 to 5 or 50 mg/m2 on days 1 and 2. For CEB patients, the carboplatin dose was calculated from the glomerular filtration rate to achieve a serum concentration x time of 5 mg/mL x minutes. Chemotherapy was recycled at 21-day intervals to a total of four cycles. RESULTS: Of patients assessable for response, 253 of 268 (94.4%) of those allocated to receive BEP achieved a complete response, compared with 227 of 260 (87.3%) allocated to receive CEB (P = .009). There were 30 treatment failures in the 300 patients allocated to BEP and 79 in the 298 allocated to CEB (log-rank chi 2 = 26.9; P < .001), which led to failure-free rates at 1 year of 91% (95% confidence interval [CI], 88% to 94%) and 77% (95% CI, 72% to 82%), respectively. There were 10 deaths in patients allocated to BEP and 27 in patients allocated to CEB (log-rank chi 2 = 8.77; P = .003), which led to 3-year survival rates of 97% (95% CI, 95% to 99%) and 90% (95% CI, 86% to 94%), respectively. CONCLUSION: With these drug doses and schedules, combination chemotherapy based on carboplatin was inferior to that based on cisplatin. This BEP regimen that contains moderate doses of etoposide and bleomycin is effective in the treatment of patients with good-prognosis metastatic nonseminoma.

Novel treatments for metastatic renal cell carcinoma.

The mainstay of any curative treatment in renal cell carcinoma (RCC) is surgery. In case of metastatic disease at presentation a radical nephrectomy is recommended to good performance status patients prior to start of interferon-alfa treatment. Interferon-alpha (IFN-alpha) offers in a small but significant percentage of patients advantage in overall survival; interleukin-2 (IL-2) based therapy gives similar survival rates. To date hormonal and chemotherapy do not have a proven impact on survival. The recent new insights in the molecular biology of clear RCC has revealed a key-role for vascular endothelial growth factor (VEGF) in the stimulation of angiogenesis in this highly vascularized tumour. This opens interesting new treatment strategies including: blockage of VEGF with the monoclonal antibody bevacizumab and inhibition of VEGF receptor tyrosine kinases (with small oral molecules such as SU11248 or PTK787). Likewise, inhibition of the Raf kinase pathway (with oral Bay 43-9006) or inhibition of the mTOR pathway (with i.v. CCI-779) are under investigation. Preliminary clinical results with all these compounds are interesting and the results of ongoing phase III studies will become available in the next years.

The quality of chemotherapy and its quality assurance.

AIMS: Assessment of the quality of chemotherapy care and its quality assurance in clinical trials and daily practice. METHODS: Using Medline, literature was searched combining the following words: quality assurance or quality of care, combined with anti-neoplastic agents. The bibliography of each article was reviewed for additional literature. Those reports in English, French, German or Dutch focusing quality assurance or quality of care and chemotherapy were selected. RESULTS: One hundred and five articles were selected by Medline and after review and adding of additional literature 53 articles remained. In clinical trials information on quality of chemotherapy is sparse. Different cooperative groups reported on suboptimal dosing, suboptimal registration of chemotherapy and several trials indicated that suboptimal dosing led to impaired outcome. Most quality assurance activities in clinical trials are concerned with audit and feedback and on-site visits. In daily practice the quality of chemotherapy is mostly impaired by the fact that it is not given although indicated and if it is given non-evidence based chemotherapy or administration schedules and reduced dose intensity decrease the quality of care. Especially, age, comorbidity and socio-economic status reduce the chance of receiving good quality of care regarding chemotherapy. Activities mostly used for quality assurance are generation of guidelines, specialisation and multidisciplinary care. CONCLUSIONS: Most quality assurance activities in clinical trials and daily practice are directed to structure and process parameters. More evidence that quality of care is related to outcome should be sought. Quality assurance in daily practice should aim at guideline implementation, specialisation and multidisciplinary care and should pay attention especially to the older patients, patients with comorbidity and patients from lower socio-economic classes.

Phase I radioimmunotherapy of metastatic renal cell carcinoma with 131I-labeled chimeric monoclonal antibody G250.

Clinical tumor targeting studies with chimeric monoclonal antibody G250 (cG250) in renal cell carcinoma (RCC) patients indicated the potential use of this antibody for radioimmunotherapy. Here we report on a phase I activity dose escalation study to determine the safety, the maximum tolerable dose (MTD), and the possible therapeutic potential of 131I-labeled cG250 in patients with progressive metastatic RCC. All patients (n = 12) received a diagnostic i.v. infusion of 5 mg of cG250 labeled with 222 MBq of 131I. If accumulation of the antibody in metastatic lesions was observed, patients were hospitalized and a second, therapeutic, i.v. infusion of 5 mg of cG250 labeled with a high dose of 131I was administered (n = 8). Three patients per dose level were entered, starting at 1665 MBq/m2. If no dose-limiting toxicity occurred, the study continued at the next dose level (555 MBq/m2 increase). Most patients experienced mild nausea without vomiting. No other complaints were reported during hospitalization. In two of two patients who received a dose of 2775 MBq/m2, grade IV hematological toxicity was observed, which was defined as dose limiting. Thus, the MTD was set at 2220 MBq/m2. In one patient (2220 MBq/m2), stable disease (lasting 3-6 months) was achieved, whereas another patient (2220 MBq/m2) showed a partial response that is ongoing (>9 months). The minor responses observed in this phase I trial in patients with an advanced stage of RCC are encouraging and warrant further study in a phase II setting at the MTD to determine the efficacy of radioimmunotherapy for metastatic RCC.

Human leukocyte antigen expression in renal cell carcinoma lesions does not predict the response to interferon therapy.

Human leukocyte antigen (HLA) classes I and II molecules are essential for antigen presentation to cytotoxic T cells and helper T cells, respectively. Consequently, they may play a role in anticancer immunotherapy as well. We studied whether the pretreatment HLA phenotype of the tumor is predictive for response to interferon immunotherapy in vivo. Therefore, renal cell carcinoma (RCC) primary tumor lesions from 31 patients treated with interferon-alpha and interferon-gamma (13 responders and 18 nonresponders) were analyzed retrospectively for HLA antigen expression with immunohistochemical methods. Furthermore, from eight patients, pretreatment metastatic lesions were examined. In the primary tumors HLA class I expression was high: in 26 of 30 lesions more than 50% cells were stained. HLA class II expression was mostly low: in 14 of 31 primary tumors less than 5% cells were stained. A significant correlation was found between HLA phenotype of primary tumors and corresponding metastases. There was no association between tumor HLA classes I and II antigen expression and clinical response to interferon therapy. In conclusion, pretreatment HLA phenotype of RCC has no predictive value for outcome of interferon immunotherapy. A role for treatment-induced changes in HLA expression in vivo, however, can not be excluded. These findings do not provide indications for the working mechanism of interferon immunotherapy in vivo.

Clinical and immunopathological results of a phase II study of perilymphatically injected recombinant interleukin-2 in locally far advanced, nonpretreated head and neck squamous cell carcinoma.

Fifteen patients with locally far advanced, nonpretreated head and neck squamous cell carcinoma were treated with low-dose recombinant interleukin-2, using 10 daily perilymphatic injections. The therapy was well tolerated. No tumor regression was observed. Tumor biopsies were taken before and after treatment. Histopathological studies including evaluation of the mononuclear cell infiltrate and immunohistochemical detection of human leukocyte antigen (HLA) expression on tumor cells were performed. HLA class I was not detectable in 1 of 10 samples, and HLA class II expression was seen in 2 of 10 samples. As compared to pretreatment biopsies, no changes were found after treatment. This is in agreement with the lack of a clinical response.

Repetitive weekly cycles of 4-day continuous infusion of recombinant interleukin-2: a phase I study.

A phase I trial was performed with a new interleukin-2 (IL-2) given as a continuous intravenous infusion in patients with solid tumors. The objectives of the study were to examine the feasibility of administering IL-2 in 4-day cycles for 4 consecutive weeks, and to investigate the response pattern of peripheral blood lymphocytes. Tumor necrosis factor (TNF) and IL-2 serum concentrations were also measured. Prior to this study, IL-2 had been tested at increasing dosages during one 4-day cycle, and it appeared that a dose of 1300 mcg/m2/day was tolerated. However, when this treatment schedule was maintained for 4 consecutive weeks, the maximum tolerated dose was 430 mcg/m2/day. In this schedule, a dose-dependent progressive increase in rebound lymphocyte count occurred after each weekly cycle, resulting in a 5-70-fold increase after the 4th cycle. Serum TNF peak concentrations also showed a tendency to increase during each subsequent cycle, while serum IL-2 peak concentrations showed a paradoxical decrease. Clinical toxicity comprised several events, which, possibly, could be ascribed to autoimmune phenomena. Myocardial infarction as a late toxicity of IL-2 is suggested. One complete response (renal carcinoma) and two partial responses (renal and breast carcinoma) were documented, one of these occurring in a patient who previously had shown a transient response on interferon therapy.

Monocyte function is normal in quiescent psoriasis.

We report an investigation of peripheral blood monocytes from untreated patients with mild, quiescent psoriasis. Possible metabolic changes were monitored by the determination of 3 enzymes representing different pathways of glucose metabolism and 2 lysosomal enzymes. Signal processing was evaluated by the measurement of cyclic AMP levels before and after hormonal stimulation. Luminol-amplified chemiluminescence provided an objective approach to assessing phagocytic capacity. Finally, the pattern of maturation of normal and psoriatic monocytes has been compared during culture in vitro. Our results were uniformly and wholly negative; we conclude that the concept of an "intrinsic" abnormality of the psoriatic monocyte may be excluded. Possible reasons for discrepancies in the literature are discussed.

Prognostic and predictive factors of immunotherapy in metastatic renal cell carcinoma.

Metastatic renal cell carcinoma has a poor prognosis. The value of immunotherapy with IFN-alpha and IL-2 both as single agent or as the combination is extensively investigated. The optimal dose and schedule is not known. In various studies response rates vary between 10 and 40%. The duration of response is variable. For a partial response a median duration between 10 and 12 months is given. Complete responses are sometimes long-lasting (a couple of years). The toxicity is drug, dose and schedule dependent. On the basis of a number of prognostic factors, such as performance score, time between the initial diagnosis and the treatment of metastases and the number of metastatic sites, patients can be divided in different prognostic groups. Patients who are classified in the good or intermediate prognostic group may have an improvement of their survival after immunotherapy and therefore they are candidates for immunotherapy.

Quality assurance in medical oncology within the EORTC. European Organisation for Research and Treatment of Cancer.

Quality assurance (QA) lately arrived in the medical arena in comparison to other fields. EORTC focused initially its attention on the aspects related to clinical trial data handling. In the late 1980s, the EORTC appointed a Quality Control Committee (QCC) with the remit to expand the QA activities to the main disciplines involved in cancer treatment. From 1990 to 1996, two projects supported by the European Commission enabled the QCC to address, amongst others, specific questions related to medical oncology. Both projects focused on the practices of chemotherapy delivery and the quality of data reporting. Following these projects, the QCC developed standard guidelines to advise on chemotherapy delivery and also a systemic chemotherapy checklist to enable an easy collection of essential data onto the patient's files. More recently, the EORTC QA Committee proposed a minimal set of quality control procedures to be implemented by all EORTC groups.

Phase II trial of cisplatin for adenocarcinoma of unknown primary site. IKZ/IKO Clinical Research Group.

The activity of cisplatin against advanced metastatic adenocarcinoma of unknown primary site (ACUP) was evaluated in 21 patients. Cisplatin (100 mg/m2) was given as a 4-h continuous infusion every 3 weeks, with appropriate fluids and diuretics. The overall response rate was 19% with 1 complete remission for 12 months and 3 partial remissions lasting from 4 to 7 months. 7 patients achieved stable disease and in 9 patients the disease was progressive. The median duration of response was 6.5 months. The median survival 7.5 months. The median survival of the total patient group was 5 months (range 1-18 months). Toxicity comprised mainly nausea and vomiting, mild creatinine elevation and leukocytopenia. Slight ototoxicity was observed in 6 patients.