One course of adjuvant BEP in clinical stage I nonseminoma mature and expanded results from the SWENOTECA group.

BACKGROUND: SWENOTECA has since 1998 offered patients with clinical stage I (CS I) nonseminoma, adjuvant chemotherapy with one course of bleomycin, etoposide and cisplatin (BEP). The aim has been to reduce the risk of relapse, sparing patients the need of toxic salvage treatment. Initial results on 312 patients treated with one course of adjuvant BEP, with a median follow-up of 4.5 years, have been previously published. We now report mature and expanded results. PATIENTS AND METHODS: In a prospective, binational, population-based risk-adapted treatment protocol, 517 Norwegian and Swedish patients with CS I nonseminoma received one course of adjuvant BEP. Patients with lymphovascular invasion (LVI) in the primary testicular tumor were recommended one course of adjuvant BEP. Patients without LVI could choose between surveillance and one course of adjuvant BEP. Data for patients receiving one course of BEP are presented in this study. RESULTS: At a median follow-up of 7.9 years, 12 relapses have occurred, all with IGCCC good prognosis. The latest relapse occurred 3.3 years after adjuvant treatment. The relapse rate at 5 years was 3.2% for patients with LVI and 1.6% for patients without LVI. Five-year cause-specific survival was 100%. CONCLUSIONS: The updated and expanded results confirm a low relapse rate following one course of adjuvant BEP in CS I nonseminoma. One course of adjuvant BEP should be considered a standard treatment in CS I nonseminoma with LVI. For patients with CS I nonseminoma without LVI, one course of adjuvant BEP is also a treatment option.

Sperm counts and endocrinological markers of spermatogenesis in long-term survivors of testicular cancer.

BACKGROUND: The objective of this study was to assess markers of spermatogenesis in long-term survivors of testicular cancer (TC) according to treatment, and to explore correlations between the markers and associations with achieved paternity following TC treatment. METHODS: In 1191 TC survivors diagnosed between 1980 and 1994, serum-follicle stimulating hormone (s-FSH; n=1191), s-inhibin B (n=441), and sperm counts (millions per ml; n=342) were analysed in a national follow-up study in 1998-2002. Paternity was assessed by a questionnaire. RESULTS: At median 11 years follow-up, 44% had oligo- (<15 millions per ml; 29%) or azoospermia (15%). Sperm counts and s-inhibin B were significantly lower and s-FSH was higher after chemotherapy, but not after radiotherapy (RT), when compared with surgery only. All measures were significantly more abnormal following high doses of chemotherapy (cisplatin (Cis)>850 mg, absolute cumulative dose) compared with lower doses (Cis ≤ 850 mg). Sperm counts were moderately correlated with s-FSH (-0.500), s-inhibin B (0.455), and s-inhibin B : FSH ratio (-0.524; all P<0.001). All markers differed significantly between those who had achieved post-treatment fatherhood and those with unsuccessful attempts. CONCLUSION: The RT had no long-term effects on the assessed markers of spermatogenesis, whereas chemotherapy had. At present, the routine evaluation of s-inhibin B adds little in the initial fertility evaluation of TC survivors.

Gene variations in sex hormone pathways and the risk of testicular germ cell tumour: a case-parent triad study in a Norwegian-Swedish population.

BACKGROUND: Testicular germ cell tumour (TGCT) is the most common cancer in young men, and an imbalance between the estrogen and androgen levels in utero is hypothesized to influence TGCT risk. Thus, polymorphisms in genes involved in the action of sex hormones may contribute to variability in an individual's susceptibility to TGCT. METHODS: We conducted a Norwegian-Swedish case-parent study. A total of 105 single-nucleotide polymorphisms (SNPs) in 20 sex hormone pathway genes were genotyped using Sequenom MassArray iPLEX Gold, in 831 complete triads and 474 dyads. To increase the statistical power, the analysis was expanded to include 712 case singletons and 3922 Swedish controls, thus including triads, dyads and the case-control samples in a single test for association. Analysis for allelic associations was performed with the UNPHASED program, using a likelihood-based association test for nuclear families with missing data, and odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. False discovery rate (FDR) was used to adjust for multiple testing. RESULTS: Five genetic variants across the ESR2 gene [encoding estrogen receptor beta (ERß)] were statistically significantly associated with the risk of TGCT. In the case-parent analysis, the markers rs12434245 and rs10137185 were associated with a reduced risk of TGCT (OR = 0.66 and 0.72, respectively; both FDRs <5%), whereas rs2978381 and rs12435857 were associated with an increased risk of TGCT (OR = 1.21 and 1.19, respectively; both FDRs <5%). In the combined case-parent/case-control analysis, rs12435857 and rs10146204 were associated with an increased risk of TGCT (OR = 1.15 and 1.13, respectively; both FDRs <5%), whereas rs10137185 was associated with a reduced risk of TGCT (OR = 0.79, FDR <5%). In addition, we found that three genetic variants in CYP19A1 (encoding aromatase) were statistically significantly associated with the risk of TGCT in the case-parent analysis. The T alleles of the rs2414099, rs8025374 and rs3751592 SNPs were associated with an increased risk of TGCT (OR = 1.30, 1.30 and 1.21, respectively; all FDRs <5%). We found no statistically significant differences in allelic effect estimates between parental inherited genetic variation in the sex hormone pathways and TGCT risk in the offspring, and no evidence of heterogeneity between seminomas and non-seminomas, or between the Norwegian and the Swedish population, in any of the SNPs examined. CONCLUSIONS: Our findings provide support for ERß and aromatase being implicated in the aetiology of TGCT. Exploring the functional role of the TGCT risk-associated SNPs will further elucidate the biological mechanisms involved.

Long-term follow-up after risk-adapted treatment in clinical stage 1 (CS1) nonseminomatous germ-cell testicular cancer (NSGCT) implementing adjuvant CVB chemotherapy. A SWENOTECA study.

BACKGROUND: To offer minimized risk-adapted adjuvant treatment on a community and nationwide basis for patients with clinical stage 1 (CS1) nonseminomatous germ-cell testicular cancer (NSGCT). The aim was to reduce the risk of relapse and thereby reducing the need of later salvage chemotherapy while maintaining a high cure rate. PATIENTS AND METHODS: From July 1995 to January 1998, a total of 232 Swedish and Norwegian patients were treated for CS1 NSGCT. All were eligible for inclusion into one of two community-based multicenter Swedish and Norwegian Testicular Cancer Project (SWENOTECA) III studies. One study was a prospective randomized study for patients without vascular invasion in the testicular tumor (VASC-), evaluating the effect of one adjuvant course of cisplatin, vinblastine and bleomycin (CVB) compared with surveillance. The second study was a prospective study evaluating the effect of two adjuvant courses of CVB for VASC+ patients. RESULTS: Due to slow accrual and emerging data on toxicity of CVB, the studies were prematurely closed for inclusion in 1998. Of the 232 CS1 patients treated during the study period, only 97 were included in the studies. As all remaining patients were managed according to the SWENOTECA III protocol, although not randomized, the data were pooled. At a median follow-up of 10.1 years, there have been 24 relapses. While one course of CVB to VASC- patients had limited effect on the relapse rate, two courses of adjuvant CVB reduced the relapse rate among VASC+ patients by >90%. Toxicity was high in patients administered adjuvant CVB as 24% of patients experienced grade 3 or 4 obstipation/ileus and 23% grade 3 or 4 infection. CONCLUSIONS: There was no statistical difference in relapse rate between one course of adjuvant CVB and surveillance for VASC- NSGCT patients. Two courses of adjuvant CVB for VASC+ NSGCT patients reduced the relapse rate with >90% in comparison to the surveillance group. Toxicity was unacceptably high for all patients receiving CVB. Adjuvant CVB chemotherapy has no place in the treatment of CS1 NSGCT.

Predicted cardiovascular mortality and reported cardiovascular morbidity in testicular cancer survivors.

INTRODUCTION: We examined if testicular cancer (TC) treatment is associated with any risk for cardiovascular morbidity or predicted mortality according to the SCORE model, in which a 10-year future risk of >or=5% for developing a fatal cardiovascular event qualify for high-risk status. METHODS: One thousand one hundred thirty-four TC survivors treated 1980-1994 participated in this study (1998-2002). Patients were categorised in four treatment groups: surgery (n = 225), radiotherapy (n = 445), and two chemotherapy groups: cumulative cisplatin dose 850 mg (cis>850, n = 89). Patients with cardiovascular disease, diabetes or SCORE >or=5% constituted a high-risk group, and those with SCORE >1% an intermediate/high risk group. RESULTS: Age-adjusted mean SCORE was 0.93% for the surgery group. In comparison, chemotherapy treated patients had significantly higher SCORE (1.07%, p = 0.01). Only 15% of patients were scored to be at high-risk, while 53% qualified for the intermediate/high risk group. Patients in the cis>850 group had increased odds for having intermediate/high risk, compared with the surgery group (OR 3.4, 95% CI 1.3-8.7). Only 23 cardiovascular events had occurred since the testicular cancer diagnosis. CONCLUSION: The SCORE model indicates that patients treated with cisplatin-based chemotherapy have a significantly increased future risk of a fatal cardiovascular event. IMPLICATIONS FOR CANCER SURVIVORS: TC survivors should be followed regularly with respect to cardiovascular risk profile beyond the routine 10-year clinical follow-up.

Components of the metabolic syndrome in long-term survivors of testicular cancer.

BACKGROUND: A possible explanation of the excess cardiovascular risk in testicular cancer (TC) survivors is development of metabolic syndrome. The association between metabolic syndrome and TC treatment is examined in long-term survivors. PATIENTS AND METHODS: In a national follow-up study (1998-2002), 1463 TC survivors (diagnosed 1980-1994) participated. Patients >60 years were excluded in the present study, leaving 1135 patients eligible. The patients were divided in four treatment groups: surgery (n = 225); radiotherapy (n = 446) and two chemotherapy groups: cumulative cisplatin dose (Cis) 850 mg (n = 88). A control group consisted of 1150 men from the Tromsø Population Study. Metabolic syndrome was defined according to a modified National Cholesterol Education Program definition. RESULTS: Both chemotherapy groups had increased odds for metabolic syndrome compared with the surgery group, highest for the Cis >850 group [odds ratio (OR) 2.8, 95% confidence interval (CI) 1.6-4.7]. Also, the Cis >850 group had increased odds (OR 2.1, 95% CI 1.3-3.4) for metabolic syndrome compared with the control group. The association between metabolic syndrome and the Cis >850 group was strengthened after adjusting for testosterone, smoking, physical activity, education and family status. CONCLUSION: TC survivors treated with cisplatin-based chemotherapy have an increased risk of developing metabolic syndrome compared with patients treated with other modalities or with controls.

Blood pressure and body mass index in long-term survivors of testicular cancer.

PURPOSE: To evaluate blood pressure and body mass index (BMI) in long-term survivors of testicular cancer (TC) treated with different modalities. PATIENTS AND METHODS: One thousand eight hundred fourteen patients treated for unilateral TC in Norway (1980 to 1994) were invited to participate in a follow-up study (1998 to 2002), including measurements of systolic blood pressure (SBP), diastolic blood pressure (DBP), and BMI. Of these patients, 1,289 patients (71%) participated in the study. The patients were categorized into four treatment groups: surgery (n = 242), radiotherapy (n = 547), and two chemotherapy groups, cumulative cisplatin dose < or = 850 mg (n = 402) and cumulative cisplatin dose more than 850 mg (n = 98). A control group consisted of healthy males from the Tromsø Population Study (n = 2,847). RESULTS: At diagnosis, age-adjusted regression analyses showed no differences between the treatment groups for any variables. After a median follow-up time of 11.2 years, age-adjusted SBP and DBP were significantly higher for both chemotherapy groups compared with the surgery group. Chemotherapy-treated patients had increased odds for hypertension at follow-up compared with the surgery group, and the odds were highest for the cisplatin more than 850 mg group (odds ratio = 2.4; 95% CI, 1.4 to 4.0). The cisplatin more than 850 mg group had a significantly higher 10-year BMI increase and a higher prevalence of obesity at follow-up than the surgery group. Compared with healthy controls, chemotherapy-treated patients had, at follow-up, increased SBP, increased DBP, excessive BMI increase, and a higher prevalence of hypertension. CONCLUSION: Five to 20 years after therapy, cured TC patients treated with cisplatin-based chemotherapy had significantly higher levels of blood pressure, a higher prevalence of hypertension, and an excessive weight gain compared with patients treated with other modalities and compared with healthy controls.

European consensus on diagnosis and treatment of germ cell cancer: a report of the European Germ Cell Cancer Consensus Group (EGCCCG).

Germ cell tumour is the most frequent malignant tumour type in young men with a 100% rise in the incidence every 20 years. Despite this, the high sensitivity of germ cell tumours to platinum-based chemotherapy, together with radiation and surgical measures, leads to the high cure rate of > or = 99% in early stages and 90%, 75-80% and 50% in advanced disease with 'good', 'intermediate' and 'poor' prognostic criteria (IGCCCG classification), respectively. The high cure rate in patients with limited metastatic disease allows the reduction of overall treatment load, and therefore less acute and long-term toxicity, e.g. organ sparing surgery for specific cases, reduced dose and treatment volume of irradiation or substitution of node dissection by surveillance or adjuvant chemotherapy according to the presence or absence of vascular invasion. Thus, different treatment options according to prognostic factors including histology, stage and patient factors and possibilities of the treating centre as well may be used to define the treatment strategy which is definitively chosen for an individual patient. However, this strategy of reduction of treatment load as well as the treatment itself require very high expertise of the treating physician with careful management and follow-up and thorough cooperation by the patient as well to maintain the high rate for cure. Treatment decisions must be based on the available evidence which has been the basis for this consensus guideline delivering a clear proposal for diagnostic and treatment measures in each stage of gonadal and extragonadal germ cell tumour and individual clinical situations. Since this guideline is based on the highest evidence level available today, a deviation from these proposals should be a rare and justified exception.

Knowledge of and attitudes toward complementary and alternative therapies; a national multicentre study of oncology professionals in Norway.

This study reports on oncology professionals' knowledge and attitude toward complementary and alternative medicines (CAM), classified according to their primary application as complementary or alternative methods. In June 2002, we conducted a national, multicentre survey of 828 Norwegian oncologists, nurses, clerks and therapeutic radiographers. A response rate of 61% was achieved. Only a few physicians (4%) described their reactions to alternative medicine as positive compared with nurses (33%), therapeutic radiographers (32%) and clerks (55%) (P<0.0001). Females showed a more positive view than males (33% versus 14%, P<0.0001). More participants expressed a positive attitude to complementary versus alternative medicines. Most respondents regarded healing by hand or prayer, homeopathy, and Iscador (mistletoe) as alternative therapies. In contrast, most respondents classified acupuncture, meditation, reflexology, music/art-therapy, aromatherapy and massage as complementary therapies. This survey demonstrates major differences, by gender as well as oncology health profession in views about and the classification of various CAM methods.

Use of complementary and alternative therapies: a national multicentre study of oncology health professionals in Norway.

GOALS OF WORK: It is well documented that an increasing proportion of cancer patients today use complementary and alternative medicine, mostly alongside conventional therapies. This study investigates the use of complementary and alternative medicine among oncology health workers and the reported effects. PATIENTS AND METHODS: In June 2002, we conducted a national multicentre survey including 828 Norwegian oncologists, nurses, clerks and therapeutic radiographers. The response rate was 61.5%. MAIN RESULTS: We found that females were more often users of both complementary and alternative methods than males (39% versus 15% and 47% versus 17%) and that few oncologists had tried such treatments compared to nurses, therapeutic radiographers and clerks (20/12% versus 50/40%, 41/33%,and 31/50%). Interestingly, the majority of those who had tried unconventional methods reported some or very good effects. Acupuncture, homeopathy, aromatherapy and massage were the most popular therapies. Sub-group analyses including only oncologists showed that female physicians were more often users of both complementary and alternative methods compared to males (33% versus 12%, 25% versus 3%). Moreover, participants below the age of 35 years and Christians more often reported use. CONCLUSIONS: This survey demonstrates that significant proportion of oncology health workers in Norway have used non-proven therapies and that most have had a positive experience. Differences in use is highly dependent on gender, profession, age and religion.

The level of physical activity in long-term survivors of testicular cancer.

The aim of this study was to estimate the level of physical activity (LPA) in a large cohort of testicular cancer survivors (TCSs) and compare these results with observations from men in the same age range in the general population (GenPop). We also wanted to identify parameters that influenced physical activity. The study populations consisted of 1276 TCSs treated with surgery, radiotherapy or chemotherapy with or without surgery (mean observation time was 12 years), and 20391 male inhabitants from a Norwegian county (GenPop). All completed a question investigating two sub-levels of physical activity. The logistic regression analysis adjusting for different covariates, showed significantly more physically active men among the TCSs compared with the GenPop (43 versus 37%) (adjusted odds ratio (aOR)=1.32 (95% Confidence Interval (CI) 1.10-1.58)). The results indicate that the experience of testicular cancer increases rather than reduces the LPA in TCSs, independent of treatment given.

Does prophylactic breast irradiation prevent antiandrogen-induced gynecomastia? Evaluation of 253 patients in the randomized Scandinavian trial SPCG-7/SFUO-3.

OBJECTIVES: To examine the development of antiandrogen-induced gynecomastia and breast tenderness in the first 253 patients in a randomized Scandinavian trial (SPCG-7/SFUO-3) with a 12-month complete follow-up evaluation performed by both doctors and patients. METHODS: In this study, the treating doctor and patient decided whether prophylactic irradiation (RT) of the breast should be given to prevent antiandrogen-induced gynecomastia. At each visit, the doctor evaluated the occurrence of gynecomastia and breast tenderness. Questions about gynecomastia and breast tenderness were also included in the study quality-of-life questionnaire (Prostate Cancer Symptom Scale). RESULTS: Mammary RT with mostly single fraction (12 to 15 Gy) electrons was given to 174 (69%) of the 253 evaluated patients. At the 1-year follow-up visit, the doctor evaluations indicated some form of gynecomastia in 71% and 28% (P <0.001) of the nonirradiated (no-RT) and irradiated (RT) patients, respectively. The patient evaluations at 1 year showed some form of breast enlargement in 78% and 44% (P <0.001) of the no-RT and RT patients, respectively. The doctors reported some form of breast tenderness at 1 year in 75% and 43% (P <0.001) of the no-RT and RT patients, respectively. The patient evaluations of breast tenderness show an expected significant increase in the RT arm at the 3-month follow-up, which was probably due to skin reactions. At 1 year, significantly more patients who marked "very much" on the Prostate Cancer Symptom Scale were seen in the no-RT group. A weak correlation between the doctors' and patients' detection of breast problems was observed. CONCLUSIONS: The results show that, with high significance, prophylactic RT of the breast decreases the risk of antiandrogen-induced gynecomastia and breast tenderness.

Digitoxin medication and cancer; case control and internal dose-response studies.

BACKGROUND: Digitoxin induces apoptosis in different human malignant cell lines in vitro. In this paper we investigated if patients taking digitoxin for cardiac disease have a different cancer incidence compared to the general population. METHODS: Computer stored data on digitoxin concentrations in plasma from 9271 patients with cardiac disease were used to define a user population. Age and sex matched controls from the Norwegian Cancer Registry were used to calculate the number of expected cancer cases. RESULTS: The population on digitoxin showed a higher incidence of cancer compared to the control population. However, an additional analysis showed that the population on digitoxin had a general increased risk of cancer already, before the start on digitoxin. Leukemia/lymphoma were the cancer types which stood out with the highest risk in the digitoxin population before starting on digitoxin. This indicates that yet unknown risk factors exist for cardiovascular disease and lymphoproliferative cancer. An internal dose-response analysis revealed a relationship between high plasma concentration of digitoxin and a lower risk for leukemia/lymphoma and for cancer of the kidney/urinary tract. CONCLUSION: Morbidity and mortality are high in the population on digitoxin, due to high age and cardiac disease. These factors disturb efforts to isolate an eventual anticancer effect of digitoxin in this setting. Still, the results may indicate an anticancer effect of digitoxin for leukemia/lymphoma and kidney/urinary tract cancers. Prospective clinical cancer trials have to be done to find out if digitoxin and other cardiac glycosides are useful as anticancer agents.

EAU guidelines on testicular cancer.

OBJECTIVES: To establish guidelines for the diagnosis, staging, treatment and follow-up of germ cell testicular cancer. METHODS: A search of published work was conducted using Medline. Highly evidence-based articles were selected and their findings analysed by the members of the Oncological Urology Working Group of the EAU. Testis cancer is rare and affects young men in their 3rd and 4th decades of life. The majority of these tumours are derived from germ cells (seminomatous and non-seminoma germ cell testicular cancer), and more than 50% of patients are diagnosed with stage I disease. Epidemiological, pathological and clinical risk factors are well established. The tumour, node, metastasis (TNM) staging system is endorsed, and for metastatic disease a recently devised prognostic-factor-based staging system has proven to be useful. Staging assessment includes pre- and post-orchiectomy marker levels, pathology of the testis, and nodal and visceral status. Following orchiectomy, treatment depends on the tumour type, pathological risk factors for stage I disease and clinical prognostic factors for advanced disease. The cure rate is excellent for disease stages I and II, irrespective of the treatment adopted. However, the pattern of relapse (rate, timing and site) is highly influenced by therapeutic policy. For metastatic disease, survival depends on clinical prognostic factors and treatment. Follow-up schedules are tailored according to stage, tumour type and post-orchiectomy treatment schedules. CONCLUSIONS: Excellent cure rates are achieved for early-stage germ cell testis tumours following accurate staging at diagnosis. Satisfactory survival rate can be achieved in advanced metastatic disease using a multidisciplinary therapeutic approach. Follow-up schedules vary, depending on the pathology and stage of the primary tumour and on the treatment policy adopted following orchiectomy.

Risk-adapted treatment of clinical stage 1 non-seminoma testis cancer.

250 patients with clinical stage 1 non-seminomatous germ cell tumours of the testis (NSGCT 1) were included into a prospective multicentre protocol during 1990-1994 and treated according to three risk strata: patients without tumour cell invasion of vascular structures in the testis (VASC-) and elevated serum AFP levels (AFP+) at orchiectomy were considered low risk (LR) and only observed closely. VASC- and AFP- or VASC+ and AFP+ patients were presumed intermediate risk (IR) and pathologically staged (PS) by retroperitoneal lymph node dissection (RPLND). VASC+ and AFP-patients were regarded as high risk (HR) and received adjuvant chemotherapy (PEB x 3). At a median observation time of 40 (7-68) months, all patients were alive and without evidence of active germ cell cancer. The actuarial relapse rate in the 106 LR patients was 22%, and 70% (14/20) had elevated serum tumour markers at relapse. One of 32 (3%) HR patients relapsed with a resectable retroperitoneal mature teratoma despite adjuvant chemotherapy. Only 14% of the 99 IR patients who underwent RPLND had PS2 disease, and the actuarial relapse rate in 85 PS1 patients was 18%. This multicentre study demonstrated that excellent therapeutic outcome is possible when 18 comparatively small urological and oncological centres follow a strict and formal cancer care programme. The useful prognostic effect of VASC was once again verified. Pathological staging by RPLND in NSGCT1 is, in our opinion, not necessary, with presumed low-risk patients offered surveillance and high-risk patients offered adjuvant chemotherapy.

Treatment intention in hospitalized cancer patients in oncological wards in Norway: a national survey.

Clinicians often do not agree whether a treatment is given with a palliative or curative intent. A common clear definition does not exist. This study has assessed the usefulness of dividing the goal of treatment into three distinct categories: curative treatment; palliative, symptom preventive treatment; and palliative, symptom relieving treatment. In a cross-sectional study among all cancer centres in Norway, a total of 629 patients were included into the study. Of these patients, 60% received palliative treatment, with an equal distribution between symptom preventive and symptom relieving. The definitions were found easy to use by the physicians. It gave important information of differences between cancer diagnosis with respect to the number of patients receiving palliative treatment. In order to refine the classification system, the authors will, in future studies, include a fourth category, life prolonging treatment, which is located between curative and palliative treatment with respect to treatment intensity.

Phase II trial of anaxirone (TGU) in advanced colorectal cancer: an EORTC Early Clinical Trials Group (ECTG) study.

Anaxirone, a rationally synthesised triepoxide derivative, was given to 46 patients with metastatic colorectal cancer. Good risk patients received 800 mg/m2 as a rapid intravenous injection every 4 weeks, whereas poor risk patients received 650 mg/m2. Of 46 patients, 45 were evaluable for toxicity and 42 for efficacy analysis. There were 37/45 patients with poor risk, showing no difference in toxicity as compared to good risk patients. The major toxic effect was myelosuppression with 34% of all patients experiencing grade 3 or 4 leucopenia; thrombocytopenia was less frequent. Locoregional phlebitis occurred in 66% of the patients. There was no objective tumour response to anaxirone in 42 evaluable patients. Only 4 patients achieved stabilisation of the disease lasting maximally up to 248 days. Anaxirone is inactive in metastatic colorectal cancer.

Toxicity in long-term survivors after adriamycin containing chemotherapy of malignant germ-cell tumors.

In order to assess overall treatment-induced long-term morbidity after high-dose adriamycin-based chemotherapy +/- radiotherapy, clinically significant toxicity was studied in survivors after treatment of advanced germ-cell cancer who had received adriamycin-containing chemotherapy before cisplatin became available in Norway. Most of the patients were also irradiated. The study comprises 47 patients with advanced germ-cell cancer who survived for at least 5 years after chemotherapy containing adriamycin (VACAM: vincristine, adriamycin, cyclophosphamide, actinomycin-D and medroxyprogesterone acetate) as part of their primary systemic treatment (before 1978) or as maintenance chemotherapy after initial cisplatin-based cytotoxic treatment (after 1978). Thirty-two patients also had radiotherapy. The median follow-up was 12.3 years. Forty-one events of late toxicities were recorded in 25 patients, 37 of these were observed after combined radiotherapy and chemotherapy. The most frequent late side effects were cardiotoxicity, gastrointestinal toxicity and neurological disorders observed in 7, 12 and 8 patients, respectively. Three patients who were irradiated to the cardiac region, died of heart failure. Secondary solid cancer developed in 7 patients after a median follow-up of 10.5 years (relative risk 4.8, 95% confidence interval 1.9 to 9.9). In a historical perspective high-dose adriamycin-containing combination chemotherapy if applied with cyclophosphamide and/or radiotherapy, may occasionally be curative in selected patients with advanced germ cell tumours, but leads to an unacceptable high incidence of severe cardiac, gastrointestinal and neurological late side effects. The present follow-up study highlights that such treatment should be avoided in the curatively intended treatment of cancer patients and emphasizes the need of long-term follow-up studies in surviving cancer patients.

[Treatment of anal cancer in Trøndelag]. / Behandling av cancer ani i Trøndelag.

We have retrospectively examined the medical records and prospectively studied the survival of 43 patients (37 women and six men) treated for anal cancer in the Trøndelag region of Norway during the period 1970-89. During this period, different strategies were used, ranging from primary surgery to combined chemo-radiotherapy and sphincter saving therapy. 20 patients were treated with surgery alone, nine patients first with surgery and postoperatively with irradiation because the surgery was non-radical (histologic), and 14 patients with combined chemo- and radiotherapy. The five year cancer ani-specific survival in the whole group is 69%. The predicted five year survival in the chemo-radiotherapy group is 90% versus 61% in the group treated with surgery. Primary chemotherapy combined with radiotherapy should be the preferred treatment for carcinoma of the anal canal.