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1.
Br J Cancer ; 94(7): 947-54, 2006 Apr 10.
Article in English | MEDLINE | ID: mdl-16570051

ABSTRACT

This multicentre, open-label, controlled clinical trial assessed the effects of epoetin alfa treatment on haematologic and quality of life (QOL) parameters in 182 anaemic (Hb< or = 12 g dl(-1)) ovarian cancer patients receiving platinum chemotherapy. Patients were randomised 2 : 1 to receive epoetin alfa 10,000-20 000 IU three times weekly plus best standard treatment (BST) or BST only. Main study end points were changes from baseline in haemoglobin (Hb) level, transfusion requirements, and QOL. For the epoetin alfa group, mean Hb increased by 1.8 g dl(-1) by weeks 4-6 and was significantly increased from baseline through study end (P<0.001). The mean change in Hb from baseline was significantly (P<0.001) greater for epoetin alfa than BST patients at all post-baseline evaluations. Significantly fewer epoetin alfa than BST patients required transfusion(s) after the first 4 weeks of treatment (7.9 vs 30.5%; P<0.001). Also, significant (P< or = 0.04) differences favouring the epoetin alfa group over the BST group were found for all three median CLAS scores (Energy Level, Ability to Do Daily Activities, Overall QOL) and the median average CLAS score during chemotherapy. These findings support use of epoetin alfa to increase Hb levels, reduce transfusion use, and improve QOL in anaemic ovarian cancer patients receiving platinum chemotherapy.


Subject(s)
Blood Transfusion , Erythropoietin/therapeutic use , Hematinics/therapeutic use , Hemoglobins/analysis , Ovarian Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Cisplatin/adverse effects , Cisplatin/therapeutic use , Epoetin Alfa , Female , Humans , Middle Aged , Ovarian Neoplasms/complications , Ovarian Neoplasms/pathology , Quality of Life , Recombinant Proteins
2.
Int J Gynecol Cancer ; 16 Suppl 1: 18-24, 2006.
Article in English | MEDLINE | ID: mdl-16515562

ABSTRACT

Current accepted prognostic indicators in ovarian cancer include performance status, surgical (FIGO) staging, and residual disease after operation. Here we present data from a prospective analysis of patients with ovarian cancer treated at the Christie Hospital. We confirm the independent prognostic effects of FIGO staging, performance status, and residual disease in our group of patients and furthermore show that CA125 levels at presentation to the oncology service are of independent prognostic significance (P= 0.02). We present survival data and show that the 3-year, cancer-specific survival for stage I disease is 90%. We postulate that this good survival may in part be due to the use of computed tomography scanning at presentation to allow accurate staging. Further clinical trials are needed to test whether combinations of surgical, histologic, biochemical, and radiologic parameters can be used to identify a population with such a good prognosis that adjuvant therapy is not required.


Subject(s)
Adenocarcinoma/mortality , Ovarian Neoplasms/mortality , Adenocarcinoma/blood , Adenocarcinoma/diagnosis , Adult , Aged , Aged, 80 and over , CA-125 Antigen/blood , Cancer Care Facilities/statistics & numerical data , Female , Humans , Middle Aged , Neoplasm Staging , Neoplasm, Residual , Ovarian Neoplasms/blood , Ovarian Neoplasms/diagnosis , Prognosis , Prospective Studies , Severity of Illness Index , Survival Analysis , Tomography, X-Ray Computed , United Kingdom/epidemiology
3.
Br J Cancer ; 94(1): 55-61, 2006 Jan 16.
Article in English | MEDLINE | ID: mdl-16404360

ABSTRACT

The feasibility of combination irinotecan, carboplatin and docetaxel chemotherapy as first-line treatment for advanced epithelial ovarian carcinoma was assessed. One hundred patients were randomised to receive four 3-weekly cycles of carboplatin (area under the curve (AUC) 7) followed by four 3-weekly cycles of docetaxel 100 mg m(-2) (arm A, n=51) or docetaxel 60 mg m(-2) with irinotecan 200 mg m(-2) (arm B, n=49). Neither arm met the formal feasibility criterion of an eight-cycle treatment completion rate that was statistically greater than 60% (arm A 71% (90% confidence interval (CI) 58-81%; P=0.079; arm B 67% (90% CI 55-78%; P=0.184)). Median-dose intensities were >85% of planned dose for all agents. In arms A and B, 15.6 and 12.2% of patients, respectively, withdrew owing to treatment-related toxicity. Grade 3-4 sensory neurotoxicity was more common in arm A (1.9 vs 0%) and grade 3-4 diarrhoea was more common in arm B (0.6 vs 3.5%). Of patients with radiologically evaluable disease at baseline, 50 and 48% responded to therapy in arms A and B, respectively; at median 17.1 months' follow-up, median progression-free survival was 17.1 and 15.9 months, respectively. Although both arms just failed to meet the formal statistical feasibility criteria, the observed completion rates of around 70% were reasonable. The addition of irinotecan to first-line carboplatin and docetaxel chemotherapy was generally well tolerated although associated with increased gastrointestinal toxicity. Further exploratory studies of topoisomerase-I inhibitors in this setting may be warranted.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma/drug therapy , Fallopian Tube Neoplasms/drug therapy , Ovarian Neoplasms/drug therapy , Peritoneal Neoplasms/drug therapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Area Under Curve , Camptothecin/administration & dosage , Camptothecin/analogs & derivatives , Carboplatin/administration & dosage , Carcinoma/pathology , Disease Progression , Docetaxel , Drug Administration Schedule , Fallopian Tube Neoplasms/pathology , Female , Humans , Infusions, Intravenous , Irinotecan , Middle Aged , Ovarian Neoplasms/pathology , Peritoneal Neoplasms/pathology , Survival Analysis , Taxoids/administration & dosage , Treatment Outcome
4.
Br J Cancer ; 91(4): 639-43, 2004 Aug 16.
Article in English | MEDLINE | ID: mdl-15266327

ABSTRACT

Trastuzumab is an effective treatment for patients with metastatic breast cancer (MBC) that overexpresses HER-2. A high incidence of brain metastases (BM) has been noted in patients receiving trastuzumab. A retrospective chart review was conducted of 100 patients commencing trastuzumab for metastatic breast cancer from July 1999 to December 2002, at the Christie Hospital. Seven patients were excluded; five patients developed central nervous system metastases prior to starting trastuzumab, and inadequate data were available for two. Out of the remaining 93 patients, 23 (25%) have developed BM to date. In all, 46 patients have died, and of these 18 (39%) have been diagnosed with BM prior to death. Of the 23 patients developing BM, 18 (78%) were hormone receptor negative and 18 (78%) had visceral disease. Univariate analysis showed a significant association between the development of cerebral disease and both hormone receptor status and the presence of visceral disease. In conclusion, a high proportion of patients with MBC treated with trastuzumab develop symptomatic cerebral metastases. HER-2-positive breast cancer may have a predilection for the brain, or trastuzumab therapy may change the disease pattern by prolonging survival. New strategies to address this problem require investigation in this group of patients.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Antineoplastic Agents/therapeutic use , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Central Nervous System Neoplasms/secondary , Adult , Aged , Antibodies, Monoclonal, Humanized , Central Nervous System Neoplasms/epidemiology , Female , Humans , Incidence , Middle Aged , Receptor, ErbB-2/analysis , Receptors, Estrogen , Receptors, Progesterone , Retrospective Studies , Risk Factors , Trastuzumab
5.
Br J Cancer ; 88(5): 654-7, 2003 Mar 10.
Article in English | MEDLINE | ID: mdl-12618869

ABSTRACT

We report our experience in the management of patients with carcinosarcoma of the ovary, a rare but aggressive variant of ovarian cancer. Forty patients were treated at a single centre, which is the largest reported series. The median age at diagnosis was 65 years (range 45-86) and the median Karnofsky performance (KP) status was 70. Thirty-two patients (80%) presented with FIGO stage III or IV disease. Twenty-four had heterologous and 14 homologous carcinosarcoma on review of histopathology, but there was no significant difference in survival between these groups (P=0.28). Twenty-seven of the 40 patients had bulk residual disease present after surgery and this was associated with a worse prognosis (P=0.045). Chemotherapy was given to 32 patients (80%) of whom 26 (81%) received platinum-based regimens. Of these 32 patients, three (9.4%) achieved a complete response (CR), 10 (31%) a partial response (PR), five (16%) had stable disease, 10 (31%) had progressive disease and four were not assessable. Of the 19 patients who had a CR, PR or stable disease after chemotherapy or were unevaluable (stage Ic), the median survival was 29.6 months. Currently, seven patients are still alive although one has cancer. The overall censored median survival was 8.7 months after a median follow-up of 34 months, and the 1- and 5-year survival were 40 and 7.5%, respectively.


Subject(s)
Antineoplastic Agents/therapeutic use , Carcinosarcoma/drug therapy , Ovarian Neoplasms/drug therapy , Aged , Aged, 80 and over , Antineoplastic Agents/administration & dosage , Carcinosarcoma/pathology , Disease-Free Survival , Female , Humans , Middle Aged , Ovarian Neoplasms/pathology , Recurrence , Survival Analysis
6.
J Clin Oncol ; 20(13): 2988-94, 2002 Jul 01.
Article in English | MEDLINE | ID: mdl-12089229

ABSTRACT

PURPOSE: To test the hypothesis that a chemotherapy regimen of relatively low toxicity and 11 weeks' duration (doxorubicin, cyclophosphamide, etoposide, vincristine, bleomycin, and prednisolone [VAPEC-B]) is at least as effective in terms of disease control as 6 months' treatment with chlorambucil, vinblastine, procarbazine, and prednisone/etoposide, vincristine, and doxorubicin (ChlVPP/EVA hybrid), which is associated with a high risk of permanent sterility. PATIENTS AND METHODS: Two hundred eighty-two patients with previously untreated Hodgkin's disease, clinical stages I/II (plus mediastinal bulk and/or B symptoms) and clinical stages III/IV were randomized at three United Kingdom and one Italian center to receive either six monthly cycles of ChlVPP/EVA hybrid or 11 weekly cycles of VAPEC-B. After chemotherapy and a restaging evaluation, radiotherapy was administered to sites of previous bulk or residual radiographic abnormality before patients were observed off treatment. RESULTS: Further accrual to the trial was halted at the planned third interim analysis in September 1996. After a median follow-up of 4.9 years, freedom from progression (FFP), event-free survival (EFS), and overall survival (OS) are all significantly better in the population treated with ChlVPP/EVA than VAPEC-B, where the comparative 5-year results are 82% and 62% (FFP), 78% and 58% (EFS), and 89% and 79% (OS), respectively. The superiority of ChlVPP/EVA was seen in both low-risk and intermediate/high-risk patients, although subset analysis suggested that ChlVPP/EVA and VAPEC-B produce equivalent results in the best-prognosis patients (Hasenclever score

Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Hodgkin Disease/drug therapy , Adolescent , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Bleomycin/administration & dosage , Chlorambucil/administration & dosage , Cyclophosphamide/administration & dosage , Doxorubicin/administration & dosage , Etoposide/administration & dosage , Female , Hodgkin Disease/pathology , Humans , Incidence , Italy , Male , Middle Aged , Neoplasm Staging , Neoplasms, Second Primary/chemically induced , Prednisolone/administration & dosage , Procarbazine/administration & dosage , Prognosis , Treatment Outcome , United Kingdom , Vinblastine/administration & dosage , Vincristine/administration & dosage
7.
J Clin Oncol ; 19(6): 1629-40, 2001 Mar 15.
Article in English | MEDLINE | ID: mdl-11250991

ABSTRACT

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.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Neoplasms, Germ Cell and Embryonal/drug therapy , Seminoma/drug therapy , Testicular Neoplasms/drug therapy , Adolescent , Adult , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Bleomycin/administration & dosage , Cisplatin/administration & dosage , Disease-Free Survival , Drug Administration Schedule , Etoposide/administration & dosage , Humans , Male , Middle Aged , Neoplasms, Germ Cell and Embryonal/pathology , Prognosis , Quality of Life , Seminoma/pathology , Testicular Neoplasms/pathology , Treatment Outcome
8.
Br J Cancer ; 83(12): 1623-9, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11104556

ABSTRACT

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.


Subject(s)
Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carboplatin/therapeutic use , Seminoma/drug therapy , Testicular Neoplasms/drug therapy , Antineoplastic Agents/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carboplatin/adverse effects , Cisplatin/administration & dosage , Cisplatin/adverse effects , Etoposide/administration & dosage , Etoposide/adverse effects , Follow-Up Studies , Humans , Male , Neoplasm Metastasis , Neoplasm Staging , Neutropenia/chemically induced , Survival Analysis , Thrombocytopenia/chemically induced , Time Factors , Treatment Outcome
9.
Clin Oncol (R Coll Radiol) ; 12(3): 153-7, 2000.
Article in English | MEDLINE | ID: mdl-10942331

ABSTRACT

A retrospective analysis was performed on 66 patients, aged 70 years or older, who received treatment with a weekly doxorubicin-containing regimen (VAPEC-B) for high grade non-Hodgkin's lymphoma (NHL). Two dosing schedules were employed. The choice of regimen was at the discretion of the treating clinician and reflected the performance status of the patient and the predicted tolerance to chemotherapy. Forty-nine patients received a half-dose schedule and 17 the full-dose schedule. Those receiving the half-dose regimen had a lower median performance status and received a lower dose intensity of chemotherapy (45% versus 83%). However, the outcomes of the two groups were similar: complete remission rate 41% versus 47%, and 5-year overall survival 36% versus 23%, for the half- and full-dose groups, respectively. A similar proportion of patients (51% versus 59%) completed each regimen, although there were more delays in treatment delivery experienced in those receiving the full dose. Half-dose VAPEC-B is an effective treatment option for elderly patients with high-grade NHL and has comparable efficacy with other published regimens. The use of such low-dose doxorubicin-containing regimens in elderly patients with high-grade NHL requires further investigation.


Subject(s)
Antibiotics, Antineoplastic/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Bleomycin/administration & dosage , Cyclophosphamide/administration & dosage , Doxorubicin/administration & dosage , Etoposide/administration & dosage , Lymphoma, Non-Hodgkin/drug therapy , Vincristine/administration & dosage , Aged , Antibiotics, Antineoplastic/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Bleomycin/adverse effects , Cyclophosphamide/adverse effects , Doxorubicin/adverse effects , Drug Administration Schedule , Etoposide/adverse effects , Humans , Lymphoma, Non-Hodgkin/mortality , Retrospective Studies , Survival Rate , Vincristine/adverse effects
10.
Ann Oncol ; 11(4): 427-34, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10847461

ABSTRACT

BACKGROUND: The prognosis of patients with high-risk germ-cell cancer is poor. The toxicity and efficacy of first-line high-dose chemotherapy (HDCT) with stem-cell support was evaluated, following induction chemotherapy with BEP. PATIENTS AND METHODS: Twenty patients with poor prognosis non seminomatous germ-cell tumour by the International Consensus prognostic criteria received induction with BEP followed by one cycle of HDCT (CEC) given with carboplatin (1800 mg/m2), etoposide (1800 mg/m2), and cyclophosphamide (140 mg/kg). Of the above 20 patients only 3 received a second cycle of HDCT. Peripheral blood stem cells were infused on day 0. RESULTS: Twenty patients were assessable for toxicity and response. After a median follow-up of 27 months 15 patients (75%) are alive, 12 (60%) are disease free and 3 (15%) are alive with disease. Median survival has not been reached and overall survival at four years is 66% with a durable complete response rate of 50%. There were no deaths or cases of severe toxicity. Median time to a granulocyte count > 500/microl and platelets > 20,000/microl was 10 and 12 days respectively. Five patients have died from progressive disease 5-35 months after HDCT. CONCLUSIONS: These results support the case of first-line HDCT. The excellent toxicity profile of BEP/CEC and the two-year overall survival of 78% are encouraging and support further the ongoing randomised US intergroup study evaluating high-dose CEC after BEP.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Hematopoietic Stem Cell Transplantation , Neoplasms, Germ Cell and Embryonal/drug therapy , Adolescent , Adult , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Bleomycin/administration & dosage , Carboplatin/administration & dosage , Cisplatin/administration & dosage , Combined Modality Therapy , Cyclophosphamide/administration & dosage , Dose-Response Relationship, Drug , Drug Administration Schedule , Etoposide/administration & dosage , Female , Humans , Male , Middle Aged , Neoplasms, Germ Cell and Embryonal/pathology , Neoplasms, Germ Cell and Embryonal/therapy , Risk Factors , Survival Analysis , Treatment Outcome
11.
Br J Cancer ; 80(9): 1392-9, 1999 Jul.
Article in English | MEDLINE | ID: mdl-10424741

ABSTRACT

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.


Subject(s)
Antineoplastic Agents/therapeutic use , Cisplatin/therapeutic use , Germinoma/drug therapy , Testicular Neoplasms/drug therapy , Adolescent , Adult , Aged , Aged, 80 and over , Germinoma/mortality , Humans , Male , Middle Aged , Prognosis , Salvage Therapy , Testicular Neoplasms/mortality
13.
Cancer ; 83(7): 1409-19, 1998 Oct 01.
Article in English | MEDLINE | ID: mdl-9762943

ABSTRACT

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.


Subject(s)
Germinoma/pathology , Testicular Neoplasms/pathology , Disease-Free Survival , Follow-Up Studies , Germinoma/drug therapy , Germinoma/mortality , Germinoma/surgery , Humans , Male , Multivariate Analysis , Neoplasm Metastasis , Neoplasm, Residual/mortality , Neoplasm, Residual/pathology , Neoplasm, Residual/surgery , Prognosis , Retrospective Studies , Risk Factors , Testicular Neoplasms/drug therapy , Testicular Neoplasms/mortality , Testicular Neoplasms/surgery
14.
J Clin Oncol ; 16(8): 2601-12, 1998 Aug.
Article in English | MEDLINE | ID: mdl-9704709

ABSTRACT

PURPOSE: This was the first randomized study to investigate the efficacy of peripheral-blood progenitor cell (PBPC) mobilization using stem-cell factor (SCF) in combination with filgrastim (G-CSF) following chemotherapy compared with filgrastim alone following chemotherapy. PATIENTS AND METHODS: Forty-eight patients with ovarian cancer were treated with cyclophosphamide and randomized to receive filgrastim 5 microg/kg alone or filgrastim 5 microg/kg plus SCF. The dose of SCF was cohort-dependent (5, 10, 15, and 20 microg/kg), with 12 patients in each cohort, nine of whom received SCF plus filgrastim and the remaining three patients who received filgrastim alone. On recovery from the WBC nadir, patients underwent a single apheresis. RESULTS: SCF in combination with filgrastim following chemotherapy enhanced the mobilization of progenitor cells compared with that produced by filgrastim alone following chemotherapy. This enhancement was dose-dependent for colony-forming unit-granulocyte-macrophage (CFU-GM), burst-forming unit-erythrocyte (BFU-E), and CD34+ cells in both the peripheral blood and apheresis product. In the apheresis product, threefold to fivefold increases in median CD34+ and progenitor cell yields were obtained in patients treated with SCF 20 microg/kg plus filgrastim compared with yields obtained in patients treated with filgrastim alone. Peripheral blood values of CFU-GM, BFU-E, and CD34+ cells per milliliter remained above defined threshold levels longer with higher doses of SCF. The higher doses of SCF offer a greater window of opportunity in which to perform the apheresis to achieve high yields. CONCLUSION: SCF (15 or 20 microg/kg) in combination with filgrastim following chemotherapy is an effective way of increasing progenitor cell yields compared with filgrastim alone following chemotherapy.


Subject(s)
Antineoplastic Agents/administration & dosage , Carcinoma/therapy , Granulocyte Colony-Stimulating Factor/administration & dosage , Hematopoietic Stem Cell Mobilization , Ovarian Neoplasms/therapy , Stem Cell Factor/administration & dosage , Adult , Aged , Antigens, CD34/analysis , Antineoplastic Agents/adverse effects , Blood Component Removal , Carcinoma/blood , Colony-Forming Units Assay , Cyclophosphamide/administration & dosage , Cyclophosphamide/adverse effects , Erythroid Precursor Cells , Female , Filgrastim , Granulocyte Colony-Stimulating Factor/adverse effects , Humans , Middle Aged , Ovarian Neoplasms/blood , Recombinant Proteins , Stem Cell Factor/adverse effects
15.
Support Care Cancer ; 4(5): 378-83, 1996 Sep.
Article in English | MEDLINE | ID: mdl-8883232

ABSTRACT

The aim of this work was to measure the safety and efficacy of single i.v. doses of dolasetron mesilate for the control of emesis caused by single high-dose (at least 6 Gy) radiotherapy to the upper abdomen. The double-blind, placebo-controlled, multicenter study stratified patients on the basis of being naive or nonnaive to radiotherapy. Patients with or without a history of previous chemotherapy were enrolled. Patients were randomized to receive placebo or 0.3, 0.6, or 1.2 mg/kg dolasetron mesilate 30 min before radiotherapy, then monitored for 24 h. Antiemetic efficacy was assessed from the time to the first emetic episode or rescue, from whether there was a complete response (0 emetic episodes /no rescue medication) or a complete-plus-major response (0-2 emetic episodes/no rescue medication), from the severity of nausea (rated by patients and the investigator), and from the investigator's assessment of efficacy. Fifty patients completed the study (owing to changing medical practice, enrollment objectives were not met; consequently, no significant linear dose trend was expected). Pooled dolasetron was superior to the placebo in its effect on the time to first emesis or rescue in radiotherapy-nonnaive patients (P = 0.015). Dolasetron was statistically superior to the placebo in the overall population on the basis of a complete plus major response: 54%, 100%, 93%, and 83% for the placebo and 0.3-, 0.6-, and 1.2-mg/kg doses respectively (P = 0.002). The low response in the highest dose group may be due to an imbalance in the number of chemotherapy-nonnaive patients in that group. Dolasetron was superior to the placebo on the basis of nausea assessed by the investigator (P = 0.024) and administration of rescue medication (P = 0.006). Complete response at the 0.3-mg/ kg dose was superior to results with the placebo (P = 0.050). Treatment-related adverse events were rare, mild to moderate in intensity, and evenly distributed across the four groups. Overall, dolasetron mesilate was effective and well-tolerated in the control of single, high-dose radiotherapy-induced emesis.


Subject(s)
Antiemetics/therapeutic use , Indoles/therapeutic use , Nausea/prevention & control , Neoplasms/radiotherapy , Quinolizines/therapeutic use , Radiotherapy, High-Energy/adverse effects , Vomiting/prevention & control , Adult , Aged , Analysis of Variance , Antiemetics/administration & dosage , Double-Blind Method , Female , Humans , Indoles/administration & dosage , Injections, Intravenous , Linear Models , Male , Middle Aged , Nausea/etiology , Neoplasms/pathology , Quinolizines/administration & dosage , Treatment Outcome , Vomiting/etiology
17.
J Clin Oncol ; 14(2): 586-92, 1996 Feb.
Article in English | MEDLINE | ID: mdl-8636775

ABSTRACT

PURPOSE: To compare standard and intensive treatment strategies for patients with high-grade non-Hodgkin's lymphoma (NHL) of poor prognosis, defined by the international prognostic index. PATIENTS AND METHODS: Thirty-four patients received standard chemotherapy with 11 weeks of doxorubicin, cyclophosphamide, vincristine, bleomycin, etoposide, prednisolone, and methotrexate (VAPEC-B), and 33 received intensive treatment with 7 weeks of VAPEC-B, three cycles of ifosfamide/cytarabine, then high-dose busulfan/cyclophosphamide followed by autologous blood progenitor-cell (BPC) transplantation. RESULTS: Twelve of 33 patients in the intensive group and 26 of 34 patients in the standard group have died. The median follow-up time for the surviving patients is 31 months and 68 months, respectively. At 2 years, the actuarial estimates of event-free survival (EFS) were 61% versus 35% (P = .01) and of overall survival, 64% versus 35% (P = .01). A significant reduction in the event rate (progression or death) was maintained after adjustment for age and the number of risk factors. The estimated risk of experiencing an event was 0.37 (95% confidence interval [CI], 0.16 to 0.84) in the intensive group compared with the standard group. CONCLUSION: Patients with poor prognostic features who received high-dose therapy and BPC rescue had a superior EFS. The survival differences observed in this study justify a formal comparison in a randomized study.


Subject(s)
Hematopoietic Stem Cell Transplantation , Lymphoma, Non-Hodgkin/therapy , Adolescent , Adult , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Bleomycin/administration & dosage , Busulfan/administration & dosage , Combined Modality Therapy , Cyclophosphamide/administration & dosage , Cytarabine/administration & dosage , Etoposide/administration & dosage , Humans , Ifosfamide/administration & dosage , Lymphoma, Non-Hodgkin/mortality , Methotrexate/administration & dosage , Middle Aged , Prednisolone/administration & dosage , Prognosis , Survival Rate , Transplantation, Autologous , Vincristine/administration & dosage
18.
Cancer J Sci Am ; 1(4): 261-6, 1995.
Article in English | MEDLINE | ID: mdl-9166486

ABSTRACT

PURPOSE: Patients with ovarian cancer often experience dose-limiting myelotoxicity, nephrotoxicity and anemia following treatment with platinum-based chemotherapy. PATIENTS AND METHODS: To investigate the ability of recombinant human erythropoietin (epoetin alfa) to prevent the development of anemia, 30 patients with advanced ovarian carcinoma receiving cisplatin or carboplatin were randomly assigned to treatment with subcutaneous epoetin alfa 300 IU/kg three times a week in addition to conventional supportive treatment, or conventional supportive treatment alone, for up to six chemotherapy cycles. The dose of epoetin alfa was reduced if hemoglobin concentration exceeded 15 g/dL. RESULTS: A highly significant difference in mean hemoglobin concentrations was observed between the two groups during the first cycle of chemotherapy due to a significant decrease in mean hemoglobin concentration in the control group. A maximal difference of 3.4 g/dL was achieved during cycle three. Fewer patients required blood or platelet transfusions in the epoetin alfa-treated group, although the difference was not significant compared to the control group. Epoetin alfa was well tolerated. CONCLUSION: Epoetin alfa appears to be effective and well tolerated in preventing hemoglobin decline in patients undergoing aggressive cyclic platinum-based chemotherapy for advanced ovarian carcinoma.


Subject(s)
Anemia/drug therapy , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Erythropoietin/therapeutic use , Hematinics/therapeutic use , Neoplasms, Glandular and Epithelial/drug therapy , Ovarian Neoplasms/drug therapy , Adolescent , Adult , Aged , Anemia/blood , Anemia/chemically induced , Blood Transfusion , Carboplatin/administration & dosage , Cisplatin/administration & dosage , Epoetin Alfa , Female , Hemoglobins/metabolism , Humans , Male , Middle Aged , Neoplasms, Glandular and Epithelial/complications , Ovarian Neoplasms/complications , Quality of Life , Recombinant Proteins , Treatment Outcome
19.
J Clin Oncol ; 13(9): 2379-85, 1995 Sep.
Article in English | MEDLINE | ID: mdl-7666097

ABSTRACT

PURPOSE AND METHODS: Between December 1984 and August 1992, 423 patients with newly diagnosed Hodgkin's disease (HD) were entered onto a randomized clinical trial that compared the regimen of mechlorethamine, vinblastine, procarbazine, and prednisone (MVPP) with a doxorubicin-containing hybrid regimen (chlorambucil, vinblastine, procarbazine, and prednisone/etoposide, vincristine, and doxorubicin [ChlVPP/EVA]). Median age for the group was 29.5 years (range, 15.2 to 68.8), and 52% had bulk disease. RESULTS: After chemotherapy, patients in the hybrid arm of the trial had a higher complete remission (CR) rate (68.1% v 55.3%) and a lower failure rate (2.4% v 12.5%) than those in the MVPP arm. There were also fewer deaths during treatment in the hybrid arm of the trial (five v 13). With a median follow-up period for survivors of 4.5 years (range, 0 to 9), actuarial 5-year progression-free survival (PFS) for all cases is 80% in the hybrid arm and 66% in the MVPP arm (P = .005). A nonsignificant trend toward a better overall survival in the hybrid arm of the trial has also been identified. CONCLUSION: These results suggest that ChlVPP/EVA hybrid is superior to MVPP in the treatment of HD. It has therefore been adopted as standard first-line therapy at the two centers.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Hodgkin Disease/drug therapy , Adolescent , Adult , Aged , Chlorambucil/administration & dosage , Disease-Free Survival , Doxorubicin/administration & dosage , Etoposide/administration & dosage , Female , Follow-Up Studies , Hodgkin Disease/mortality , Humans , Male , Mechlorethamine/administration & dosage , Middle Aged , Prednisolone/administration & dosage , Procarbazine/administration & dosage , Remission Induction , Survival Rate , Vinblastine/administration & dosage , Vincristine/administration & dosage
20.
Ann Oncol ; 5(2): 147-51, 1994 Feb.
Article in English | MEDLINE | ID: mdl-7514433

ABSTRACT

UNLABELLED: BACKGROUND AND PATIENTS: A weekly schedule of chemotherapy (VAPEC-B) has been used to treat 184 consecutive patients with high grade non-Hodgkin's lymphoma (NHL). Median age for the group was 57 years (range 17-84) and 56% had stage IV disease. RESULTS: Following chemotherapy, 114 (62%) patients achieved CR or CR(u), 32 (17%) PR and 15 (8%) had not responded or progressed. Response to VAPEC-B was highly stage dependent with 70% or more of patients with stages I-III achieving CR or CR(u) but only 50% of those with stage IV. Twenty-four (15%) patients died during treatment with VAPEC-B and in 13 cases death was due to sepsis. This complication occurred mainly in patients with stage IV disease aged 60 years or older. After a median follow up period of 4.1 years, the actuarial 4 year survival for 184 patients is 45%, an overall result heavily influenced by the poor outcome for 103 patients with stage IV disease (4 year survival of 28%). Patients with earlier stage disease fared correspondingly better (44% for stage III, 68% for stage II and 80% for stage I). CONCLUSIONS: VAPEC-B gives similar results to other chemotherapy regimens currently used in the treatment of high grade NHL and has the advantage of brevity. Caution is advised in patients over the age of 60 especially in the presence of stage IV disease and dose reduction or haemopoietic growth factor support should be considered in these circumstances.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lymphoma, Non-Hodgkin/drug therapy , Adolescent , Adult , Aged , Aged, 80 and over , Bleomycin/administration & dosage , Bleomycin/adverse effects , Cyclophosphamide/administration & dosage , Cyclophosphamide/adverse effects , Doxorubicin/administration & dosage , Doxorubicin/adverse effects , Drug Administration Schedule , Etoposide/administration & dosage , Etoposide/adverse effects , Female , Humans , Lymphoma, Non-Hodgkin/mortality , Male , Middle Aged , Survival Rate , Vincristine/administration & dosage , Vincristine/adverse effects
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