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Biomedical subjects

G M Mead

Publications and source records attributed to G M Mead.

At least 37 records · Page 2Linked to original sources
PubMed2001

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.

Adolescent↗
PubMed2000

A medical research council randomized trial in patients with primary cerebral non-Hodgkin lymphoma: cerebral radiotherapy with and without cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy.

BACKGROUND: The role of chemotherapy in the treatment of patients with primary central nervous system lymphoma (PCL) remains unclear, with no randomized trials available to aid in the interpretation of the current data. The Medical Research Council therefore conducted the current randomized trial to assess the impact on survival of postradiotherapy chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) in nonimmunocompromised adult patients with pathologically proven PCL. METHODS: After surgery, patients were randomized at a ratio of 1:2 to radiotherapy alone (RT: 40 grays [Gy] in 20 fractions to the whole brain followed by a 14-Gy boost to the tumor plus a 2-cm tumor margin) or to the same radiotherapy followed by six cycles of CHOP chemotherapy given at 3-week intervals (RT-CHOP). The target sample size was 90 patients, which allowed 90% power to detect a doubling of the median survival time. RESULTS: Between 1988 and 1995, 53 patients were randomized: Fifteen patients were randomized to RT, and 38 patients were randomized to RT-CHOP. The trial closed earlier than planned through poor accrual. The median patient age was 57 years, 57% of the patients were male, and 75% of the patients had unifocal disease. The median number of chemotherapy cycles received was 6 (mean, 4 cycles). Forty-three patients have died, and the median follow-up of survivors is 5 years (range, 1-9 years). There was no evidence of a benefit from RT-CHOP with respect to overall survival (hazard ratio [HR], 1.19; 95% confidence interval, 0.51-2.76) after adjustment for prognostic factors (patient age and neurologic performance status) in an analysis in which HR > 1 favored the control (RT) group. CONCLUSIONS: CHOP has no clear role in the postradiotherapy treatment of patients with PCL. Chemotherapy is poorly tolerated and largely palliative in older, less fit patients. In younger patients, initial chemotherapy designed to penetrate the blood-brain barrier warrants further investigation.

Adult↗
PubMed2000

A medical research council randomized trial of single agent carboplatin versus etoposide and cisplatin for advanced metastatic seminoma. MRC Testicular Tumour Working Party.

The UK Medical Research Council conducted this trial of carboplatin chemotherapy in advanced seminoma to compare single agent carboplatin with a standard combination of etoposide with cisplatin. The use of single agent carboplatin was expected to be associated with reduced toxicity. A total of 130 patients with advanced seminoma were randomly assigned to treatment with either single agent carboplatin (C) at a dose of 400 mg/m(2)to be corrected for glomerular filtration rate outside the range 81-120 ml min(-1)and to be administered on day 1 of a 21 day cycle to a total of 4 cycles or to etoposide + platinum (EP). The trial was designed as an equivalence study aiming to exclude a reduction in the 3-year progression-free survival in patients allocated to carboplatin of between 10 and 15%, requiring initially a target accrual of 250 patients (90% power significance level 5% (one-sided)). The trial closed after 130 patients had been randomized following recommendation by an independent data monitoring committee. At a median follow-up time of 4.5 years, 81% of patients had been followed up for at least 3 years and 19 patients have died. The estimated PFS rate (95% Confidence Intervals (CI)) at 3 years was 71% (60-82%) in patients allocated C and 81% (71-90%) in those allocated EP; the 95% CI for the difference in 3 year PFS was - 6% to +19%. The hazard ratio of 0.64 (95% CI 0.32-1.28) favoured EP but the difference was not statistically significant (log rank chi-squared = 1.59 P = 0.21). The 3-year survival rate was 84% (75-92%) in those allocated C, and 89% (81-96%) in those allocated EP. The hazard ratio for survival was 0.85 with 95% CI, 0.35-2.10, log rank chi-squared = 0.12, P = 0.73. The trial has not demonstrated statistically significant differences in the major survival endpoints comparing single agent carboplatin with a combination of etoposide + cisplatin. This cannot be taken as an indication of equivalence since the limited size of this trial rendered it unable to exclude a 19% lower progression-free survival and survival in those treated with single agent carboplatin which would be important clinically. Standard initial chemotherapy for advanced seminoma should be based on cisplatin combinations and the role of carboplatin awaits the outcome of further studies.

Antineoplastic Agents↗
PubMed2000

Enteropathy-type intestinal T-cell lymphoma: clinical features and treatment of 31 patients in a single center.

PURPOSE: We report the clinical features and treatment of 31 patients with a diagnosis of enteropathy-type intestinal T-cell lymphoma treated at the Wessex Regional Medical Oncology Unit in Southampton between 1979 and 1996 (23 men, eight women). PATIENTS AND METHODS: Patients were identified from our lymphoma database. Details of history, physical examination, staging investigations, treatment, and outcome were taken from patient records. RESULTS: Twelve patients (35%) had a documented clinical history of adult-onset celiac disease, and a further three had histologic features consistent with celiac disease in resected areas of the small bowel not infiltrated with lymphoma. After diagnosis, 24 (77%) of the 31 patients were treated with chemotherapy; the remaining seven had surgical treatment alone. More than half were unable to complete their planned chemotherapy courses, often because of poor nutritional status; 12 patients required enteral or parenteral feeding. A response to initial chemotherapy was observed in 14 patients (complete response, n = 10; partial response, n = 4). Observed complications of treatment were gastrointestinal bleeding, small-bowel perforation, and the development of enterocolic fistulae. Relapses occurred 1 to 60 months from diagnosis in 79% of those who responded to initial therapy. Of the total 31 patients, 26 (84%) have died, all from progressive disease or from complications of the disease and/or its treatment. The actuarial 1- and 5-year survival rates are 38.7% and 19.7%, respectively, with 1- and 5-year failure-free survival rates of 19.4% and 3.2%, respectively. CONCLUSION: The prognosis for these patients is poor. This, in part, reflects late diagnosis and poor performance status at the time of presentation. The role of salvage treatments and high-dose chemotherapy at relapse is not clear. However, it is encouraging that there are five long-term survivors in our patient population.

Actuarial Analysis↗
PubMed1999

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.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Treatment outcome of patients with brain metastases from malignant germ cell tumors.

BACKGROUND: Multiinstitutional experience with the management of cerebral metastases from malignant germ cell tumors (MGCT) is presented. METHODS: Clinical data regarding brain metastases from MGCT at diagnosis (Group 1 [56 patients]) or after cisplatin-based chemotherapy (Group 2 [83 patients]) were collected retrospectively. All patients in Group 1 received "conventional" cisplatin-based chemotherapy supplemented by cerebral radiotherapy (36 patients) and/or neurosurgery (10 patients). In the patients in Group 2 cerebral metastases were detected a median of 9 months after the initiation of chemotherapy. Thirty-five patients received chemotherapy, 59 patients received radiotherapy, and 25 patients underwent neurosurgery. RESULTS: The 5-year cause specific survival rate in Group 1 was 45% (95% confidence interval [CI], 31-59%). Neurosurgery and the absence of extracerebral, nonpulmonary visceral disease, but not cerebral radiotherapy, were independent predictors of good prognosis. The 5-year cause specific survival rate in Group 2 was 12% (95% CI, 4-20%), but was 39% among patients with an isolated brain recurrence (24 patients). Radiotherapy, but not chemotherapy, represented an independent predictor of good prognosis together with brain metastases at first recurrence and the absence of extracerebral recurrence. CONCLUSIONS: Among patients with brain metastases at the time of diagnosis of an MGCT, cisplatin-based chemotherapy resulted in a 5-year cause specific survival rate of 45%, with cerebral radiotherapy having limited impact. The 5-year cause specific survival rate for all patients with brain metastases after cisplatin-based chemotherapy was 12%, but increased to 39% in patients with an isolated brain recurrence. Cerebral radiotherapy (and neurosurgery) represent essential treatment modalities for patients in whom brain metastases are diagnosed after induction chemotherapy.

Adolescent↗
PubMed1999

The management of inferior vena cava obstruction complicating metastatic germ cell tumors.

BACKGROUND: Inferior vena cava obstruction (IVCO) is a poorly characterized complication of metastatic germ cell tumor (GCT). The authors identified 31 cases to describe the clinical features, radiologic findings, complications, and treatment of this clinical entity. METHODS: Patients with GCT and IVCO were identified from case records of a GCT database. The records of 333 male patients with metastatic GCT (27% with seminoma and 73% with nonseminomatous GCTs) were screened for either clinical or computed tomography (CT) scan evidence of inferior vena cava compression or involvement. RESULTS: Thirty-one patients were identified (9.3% of patients with metastatic GCT). Common presenting symptoms were leg swelling and dilated abdominal wall veins. Approximately 29% of patients had thromboembolic complications and there was a single case of fatal pulmonary embolism. Nine patients had no clinical features at presentation but either had CT scan evidence of IVCO or developed symptoms during treatment. Right-sided testicular primary tumors were associated more frequently with IVCO compared with left-sided primary tumors (14% vs. 4% of cases of metastatic GCT, respectively). All patients had an abdominal mass measuring > 5 cm in maximum transverse dimension. CONCLUSIONS: The authors recommend careful clinical and radiologic evaluation for the presence of IVCO in cases of bulky metastatic GCT. A high index of suspicion must accompany the evaluation of a patient with a right-sided primary testicular tumor and a paracaval abdominal mass measuring > 5 cm in maximum transverse dimension. When IVCO is identified, prophylactic anticoagulation is recommended.

Adult↗
PubMed1999

Staging and prognostic factors in testicular cancer.

Germ cell cancers of the testis are rare malignancies that occur most commonly in young adult male life. These malignancies are highly curable, and adoption of sophisticated treatment strategies, related to known prognostic-based variables, has resulted in overall cure rates of approximately 95% with acceptable morbidity. These treatment approaches require a thorough knowledge of the underlying pathology and patterns of tumour spread. In recent years a number of prognostic factor-based staging classifications have evolved, each of which can accurately predict prognosis. However, in 1997, an internationally agreed-upon consensus classification applicable to both seminoma and non-seminoma was published. This classification was well validated and has now been incorporated into the TNM and American Joint Committee on Cancer (AJCC) staging systems.

Adult↗
PubMed1999

Severe pulmonary toxicity in patients treated with a combination of docetaxel and gemcitabine for metastatic transitional cell carcinoma.

BACKGROUND: Both gemcitabine and docetaxel have been associated with pulmonary toxicity when used as single agents. We report a study in which three of five cases developed pulmonary toxicity (which proved fatal in one case) when these drugs were used in combination to treat metastatic transitional cell cancer. PATIENTS AND METHODS: Three patients developed dyspnoea, in two cases associated with pulmonary infiltrates, whilst receiving the combination of gemcitabine and docetaxel in a phase I trial. The case notes of all five patients entered into this trial were studied. A literature review was undertaken to gain information on reported pulmonary toxicity with the deoxy-cytidine analogues and taxanes given alone or in combination with or without radiotherapy. RESULTS: Three patients developed delayed dyspnoea whilst receiving gemcitabine/docetaxel in combination. This settled with cessation of treatment in one patient, however in the remaining two cases significant hypoxia developed, associated radiologically with evidence of progressive pulmonary infiltrates. One of these patients developed respiratory failure after bronchoscopy and biopsy and died. His chest X-ray changes were consistent with adult respiratory distress syndrome. The transbronchial biopsy and post mortem lung histology in this patient showed diffuse alveolar damage. The remaining patient settled with high dose prednisolone but died subsequently of progressive metastatic disease. CONCLUSION: The combination of gemcitabine and docetaxel showed promising activity in this small study. The development of pulmonary symptoms in three cases with radiological lung infiltrates in two other cases was cause for concern. Patients receiving this drug combination should be closely monitored for similar problems.

Aged↗
PubMed1999

Prognostic factors in patients progressing after cisplatin-based chemotherapy for malignant non-seminomatous germ cell tumours.

The aim of this study was to define prognostic parameters for survival in patients with malignant germ cell tumours progressing after platinum-based induction chemotherapy with or without surgery. A total of 164 progressing patients (testicular: 83%, extragonadal: 17%) were identified out of 795 patients treated with platinum-based induction chemotherapy for metastatic germ cell malignancy with or without surgery. 'Progressive disease' included patients who had progressed after a previous partial or complete remission as well as patients who failed primary therapy. Salvage chemotherapy consisted of 'conventional' platinum-based chemotherapy. Prognostic factors for survival were assessed by uni- and multivariate analyses. The resulting prognostic model was validated in an independent data set of 66 similar patients. For all 164 patients the median time from start of induction chemotherapy to progression was 10 months (range: 0-99). Thirty-eight (23%) patients relapsed after 2 years. The 5-year survival rate for all progressing patients was 30% (95% confidence interval 23-38%). In the univariate analysis the following factors most importantly predicted a poor prognosis: progression-free interval < 2 years: initial poor prognosis category (MRC criteria), < CR to induction chemotherapy, initial treatment early in the 1980s and treatment given at a 'small' centre. Three prognostic factors remained in the multivariate analysis: progression-free interval, response to induction treatment and the level of serum human chronic gonadotrophin (hCG) and alpha fetoprotein (AFP) at relapse. One hundred and twenty-four patients could be classified on the basis of these characteristics, Those patients with progression-free interval < 2 years, < CR to induction chemotherapy and high markers at relapse (AFP >100 kU l(-1) or hCG >100 IU l(-1)) formed a poor prognosis group of 30 patients, none of whom survived after 3 years. Patients with at most two of these three risk factors formed a good prognosis group of 94 patients (76%) with a 47% (37-56%) 5-year survival. Thirty-eight patients from the good prognosis group with a progression-free interval of >2 years had a 2-year survival of 74% (60-88%) and 5-year survival of 61%. These prognostic groups were validated in the independent data set, in which 5-year survival rates in the good and poor risk groups were 51% and 0% respectively. One-third of patients progressing during or after platinum-based induction chemotherapy for metastatic germ cell malignancy may be cured by repeated 'conventional' platinum-based chemotherapy. Good prognosis parameters are: progression-free interval of > 2 years, CR to induction treatment and normal or low serum markers at relapse (hCG < 100 IU l(-1) and AFP < 100 kU l(-1)). The results of high-dose salvage chemotherapy should be interpreted on the background of these prognostic factors.

Adolescent↗
PubMed1999

The value of central histopathological review of testicular tumours before treatment.

OBJECTIVE: To assess the value of central histopathological review of testicular tumours. MATERIALS AND METHODS: The histopathology reports of the referring hospital and central review were compared for all referred testicular specimens (201 orchidectomies and seven testicular biopsies) from 11 hospitals in one region, between 1992 and 1997. RESULTS: There were two main findings: First, there was a major discrepancy of tumour type in 12 specimens (6%). The most frequent change (in five cases) was from seminoma to nonseminomatous germ cell tumour (NSGCT). There were also difficulties with uncommon tumours such as spermatocytic seminoma, lymphoma and adenocarcinoma. Treatment was changed as result of the altered diagnosis in eight of these 12 patients. Second, there were discrepancies of interpretation of vascular invasion in 12 of 59 NSGCTs (20%). Differences of tumour elements recognized in NSGCTs were frequent. CONCLUSIONS: The errors discovered on central histopathological review of testicular tumours were significant, though small in number. This supports the idea of central review and is consistent with the specialization recommended in the Calman-Hine cancer arrangements.

Biopsy↗
PubMed1998

Postchemotherapy residual masses in germ cell tumor patients: content, clinical features, and prognosis. Medical Research Council Testicular Tumour Working Party.

BACKGROUND: In a retrospective study that included a detailed histopathologic review, the clinicopathologic features of patients with germ cell tumors (GCT) and resectable residual masses after chemotherapy were assessed. METHODS: Histologic material from 153 patients was available for review. Recorded details included primary histologic diagnosis, location, size and number of metastases, marker levels before and after chemotherapy, and completeness of surgical excision. A median of seven histologic sections per resection were reviewed by two pathologists independently (and together when disagreement occurred). In each case, details were recorded regarding fibrosis, necrosis, hemorrhage, embryonal carcinoma (undifferentiated teratoma), yolk sac tumor, choriocarcinoma (trophoblastic tumor), differentiated teratoma (mature and immature), dysplasia in somatic tissues, and non- germ cell tumor (GCT) malignancies. The percentage of the sample that each of these components comprised was also estimated. RESULTS: The median postchemotherapy follow-up time was 7 years, and 38 of 153 patients (25%) experienced disease progression. In a multivariate analysis, incomplete resection of all residual masses (in 38 patients) and the presence of malignant elements (in 23 patients) were independent risk factors for progression. In the subset of patients in whom all masses were completely resected, the presence of embryonal carcinoma (undifferentiated teratoma) was the single most significant risk factor for progression. Seven percent of patients had this factor, which was associated with a 2-year progression free survival rate of 12.5%, compared with 88.0% where this component was absent. CONCLUSIONS: Progression free survival can be predicted well by the completeness of excision of residual masses and the presence of malignant germ cell elements. The latter confers a relatively poor prognosis even if all of these elements are completely resected.

Disease-Free Survival↗
PubMed1998

Radiological appearances of lymphomas arising from mucosa-associated lymphoid tissue (MALT) in the lung.

We review the radiological findings in 13 patients with histologically proven (n = 10) or clinically diagnosed (n = 3) lymphomas arising in mucosa-associated lymphoid tissue (MALT) of the lung. These rare B-cell lymphomas typically follow an indolent course, and many cases are still being incorrectly described in current radiological literature under the term pseudolymphoma. The patients frequently give a history of autoimmune disease involving the affected organ, and involvement of another mucosal site as part of a disseminated MALT lymphoma, is common. The radiographic patterns of pulmonary parenchymal involvement in lung MALT lymphomas have been reviewed, and correlation made with their clinical behaviour.

Adult↗
PubMed1998

Germ cell cancer and dermatomyositis.

Although the association of dermatomyositis and malignancy is well recognized, there have been few previous reports of germ cell tumours occurring in this context. Two cases of teratoma with dermatomyositis have presented at the Wessex Medical Oncology Unit in Southampton, which prompted a review of the literature.

Adult↗
PubMed1998

A randomized trial comparing methotrexate and vinblastine (MV) with cisplatin, methotrexate and vinblastine (CMV) in advanced transitional cell carcinoma: results and a report on prognostic factors in a Medical Research Council study. MRC Advanced Bladder Cancer Working Party.

Transitional cell carcinomas may arise at any site within the urinary tract and are a source of considerable morbidity and mortality. In particular, patients with metastatic disease have a poor prognosis, with less than 5% alive at 5 years. A multicentre randomized trial comparing methotrexate and vinblastine (MV) with cisplatin, methotrexate and vinblastine (CMV) in advanced or metastatic transitional cell carcinoma was conducted in the UK. From April 1991 to June 1995, 214 patients were entered by 16 centres, 108 randomized to CMV and 106 to MV. A total of 204 patients have died. The hazard ratio (relative risk of dying) was 0.68 (95% CI 0.51-0.90, P-value = 0.0065) in favour of CMV. This translates to an absolute improvement in 1-year survival of 13%, 16% in MV and 29% in CMV. The median survival for CMV and MV was 7 months and 4.5 months respectively. Two hundred and eight patients objectively progressed or died. The hazard ratio was 0.55 (95% CI 0.41-0.73, P-value = 0.0001) in favour of CMV. Two hundred and nine patients symptomatically progressed or died. The hazard ratio was 0.48 (95% CI 0.36-0.64, P-value = 0.0001) in favour of CMV. The most important pretreatment factors influencing overall survival were WHO performance status and extent of disease. These two factors were used to derive a prognostic index which could be used to categorize patients into three prognostic groups. We conclude that the addition of cisplatin to methotrexate and vinblastine should be considered in patients with transitional cell carcinoma, taking into account the increased toxicity.

Aged↗
PubMed1998

Intensive induction-sequential chemotherapy with BOP/VIP-B compared with treatment with BEP/EP for poor-prognosis metastatic nonseminomatous germ cell tumor: a Randomized Medical Research Council/European Organization for Research and Treatment of Cancer study.

PURPOSE: The aim of this randomized trial was to assess the potential therapeutic advantage of an intensive induction-sequential chemotherapy schedule (bleomycin, vincristine, cisplatin [BOP])/etoposide, ifosfamide, cisplatin, and bleomycin [VIP-B]), compared with a regimen based on bleomycin, etoposide, and cisplatin (BEP) (BEP/etoposide and cisplatin [EP]) for the treatment of patients with poor-prognosis metastatic nonseminomatous germ cell tumors (NSGCTs). PATIENTS AND METHODS: Patients had one or more of the following: a retroperitoneal mass > or = 10 cm in diameter; mediastinal or supraclavicular mass > or = 5 cm in diameter; at least 20 lung metastases (any size); liver, bone, or brain metastases; and serum beta human chorionic gonadotropin (betaHCG) > or = 10,000 IU/L or alfa fetoprotein (AFP) > or = 1,000 IU/L. A total of 380 patients were accrued between May 1990 and June 1994 into this joint Medical Research Council (MRC)/European Organization for Research and Treatment of Cancer (EORTC) trial; of these, nine patients were deemed ineligible. RESULTS: There was no significant difference between the two arms in the proportion of patients who achieved a complete response (CR) with chemotherapy alone, ie, 79 of 185 assessable patients (57%) with BEP/EP and 72 of 186 (54%) with BOP/VIP-B (P = 0.687). With a median follow-up of 3.1 years (maximum, 5.8), a total of 107 patients (28%) had progressive disease. There was no significant difference in time to first disease progression, or failure-free or overall survival between the two arms (P = 0.21, 0.101, and 0.190, respectively). The 1-year failure-free survival rates for BEP/EP and BOP/VIP-B were 60% (95% confidence interval [CI], 53% to 67%) and 53% (95% CI, 47% to 61%). Grade 3 or 4 myelosuppression, febrile neutropenia, and weight loss were more pronounced with BOP/VIP-B than with BEP/EP, and there were more toxic deaths with BOP/VIP-B than BEP/EP (18 [9%] v nine [5%]). CONCLUSION: The intensive BOP/VIP-B therapy was associated with more toxicity, but there was no evidence of an improvement in response rate or survival compared with treatment with BEP/EP.

Adolescent↗
PubMed1998

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.

Adolescent↗