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Biomedical subjects

E Franssen

Publications and source records attributed to E Franssen.

At least 55 records · Page 3Linked to original sources
PubMed1998

Phase I-II study of 5-fluorouracil, leucovorin, doxorubicin, methotrexate, and long-term oral etoposide (FLAME) in unresectable or metastatic gastric cancer.

The objective of this phase I-II study was to determine the efficacy and toxicity of combination chemotherapy with 5-fluorouracil, leucovorin, doxorubicin, methotrexate, and oral etoposide (FLAME) in patients with measurable unresectable or metastatic gastric cancer. Starting doses on the phase I study were as follows: methotrexate 50 mg/m2 intravenous bolus day 1; leucovorin 20 mg/m2 intravenous bolus days 2 through 4, starting 24 hours after the methotrexate dose; 5-fluorouracil 325 mg/m2 intravenous bolus 15 minutes after leucovorin days 2 through 4; doxorubicin 25 mg/m2 intravenous bolus day 8; and oral etoposide 50 mg/day for 14 days, starting on day 8. A new cycle started on day 28. A total of 42 patients were treated--10 patients in the phase I study and 32 patients in the phase II study. Dose-limiting toxicity was encountered in the phase I study on the second escalation step, when doxorubicin was escalated to 30 mg/m2 and 5-fluorouracil was escalated to 350 mg/m2. In the phase II study 28 patients (109 courses) were evaluable for toxicity. Neutropenia grade 3 or more was dose limiting and was documented in 12 patients (43%) during 22 treatment courses (20%). Neutropenia was associated with febrile neutropenia requiring hospitalization in four patients during five courses of therapy. Grade 3 stomatitis and grade 3 diarrhea was infrequent, documented in two patients (two courses) and three patients (four courses), respectively. All other toxicity was grade 1 and grade 2. The combined objective response rate in 38 evaluable patients entered in both studies was 23.3% (six partial responses and one complete response). Stable disease was documented in 15 patients (39.5%). The median survival for the 42 patients entered in both trials was 6.9 months (95% confidence interval, 5.9-8.5 months). The objective response rate and median survival for the combined group is comparable with that reported for the etoposide, leucovorin, and 5-fluorouracil (ELF), and 5-fluorouracil and methotrexate (FMTX) regimens in a recently reported, multicenter, phase III study.

Adenocarcinoma↗
PubMed1998

Phase II study of dexverapamil plus anthracycline in patients with metastatic breast cancer who have progressed on the same anthracycline regimen.

The purpose of this study is to evaluate whether metastatic breast cancer that has progressed on an anthracycline-containing drug regimen will subsequently respond to that identical regimen if dexverapamil, a modulator of P-glycoprotein-mediated drug resistance, is given concomitantly. Eligible patients received 180 mg/m2 dexverapamil every 6 h for 15 doses with the anthracycline administered 30 min after the seventh dose. Blood for dexverapamil levels was drawn before and 30 min after this dose. When possible, biopsies were obtained to measure mdr-1 expression by reverse transcription-PCR and by image cytometry. Of the 21 patients entered onto the trial, 20 were evaluable for response. There were two partial responses (10%) that both lasted for 6 months, and two additional patients had stable disease. Seven patients had asymptomatic cardiotoxicity consisting of hypotension (24%), bradycardia (5%), or prolongation of the P-R interval (14%). Two patients developed acute congestive heart failure, one on dexverapamil and one 10 days after stopping it. Dexverapamil did not seem to increase anthracycline toxicity. The median trough dexverapamil plus norverapamil level on day 3 was 1110 ng/ml (range, 186-3385 ng/ml), and the median peak level was 2164 ng/ml (range, 964-8382 ng/ml). There was poor correlation between reverse transcription-PCR and image cytometry for the level of mdr-1 expression. Because dexverapamil has been shown to affect doxorubicin pharmacokinetics subsequent to the initiation of this trial, it cannot be concluded that the responses seen were necessarily due to P-glycoprotein inhibition. Additional studies are necessary to determine whether mdr-1 modulators can reverse clinical drug resistance in breast cancer patients. The intrinsic cardiotoxicity of dexverapamil makes it less suitable for such studies than several other available agents.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

Management of women at increased risk for breast cancer: preliminary results from a new program.

OBJECTIVE: To examine the characteristics of malignant tumours that develop in women undergoing surveillance for increased risk for breast cancer and to identify presentation patterns in order to determine the respective roles of mammography, clinical breast examination (CBE) and breast self-examination (BSE). SETTING: Breast Diagnostic Clinic and Familial Breast Cancer Clinic at Toronto-Sunnybrook Regional Cancer Centre. PARTICIPANTS: A total of 1044 women evaluated for breast cancer risk from Oct. 1, 1990, to Dec. 31, 1996, of whom 381 were categorized as being at high risk, 204 as being at moderate risk, 401 as being at slightly increased risk and 58 as being at no appreciably increased risk. PROGRAM COMPONENTS: Comprehensive review and discussion of risk factors, clinical assessment, surveillance recommendations that include mammography, CBE and BSE, genetics consultation (Familial Breast Cancer Clinic) and psychosocial support. Data are captured prospectively, updated at each visit and audited every 3 to 6 months. PROGRAM OUTCOMES: During the study period breast cancer was diagnosed in 24 patients, 12 in the high-risk group, 4 in the moderate-risk group and 8 in the group at slightly increased risk. The mean age at diagnosis was 47 (range 32 to 82) years. Ten cases of cancer were diagnosed during surveillance (incident cancer), 5 in women under age 50. The mean length of time from initial assessment to diagnosis was 28.6 (range 12 to 51) months. Of the 24 women, 17 reported a family history of breast cancer. The mean age at diagnosis in this cohort was 45.5 years, and the diagnosis was made under age 50 in 10 patients (59%). The mean earliest age at which breast cancer was diagnosed in a family member was 42.5 years. CONCLUSIONS: These preliminary results suggest that surveillance of women at increased risk for breast cancer may be useful in detecting disease at an early stage. The regular performance of mammography, CBE and BSE appears necessary to achieve these results.

Adult↗
PubMed1997

A phase II study of leuprolide in advanced/recurrent endometrial cancer.

In order to determine the efficacy and toxicity of the gonadotrophin-releasing hormone agonist Leuprolide in the management of patients with recurrent or metastatic endometrial cancer, we performed a phase II study. Patients were included if there was clinical or radiological documentation of bidimensionally measurable recurrent or metastatic endometrial cancer that was deemed incurable. Treatment was 7.5 mg i.m. every 28 days, and was to continue for at least 2 courses until evidence of disease progression, patient requested withdrawal, or unacceptable toxicity. Twenty-five patients received Leuprolide for recurrent or metastatic endometrial cancer. The median age at study entry was 62 years, and the median time from initial diagnosis to first course of Leuprolide was 25 months. Six patients had received no systemic or radiotherapy prior to study entry, and 2 of these had not previously undergone hysterectomy. Fifteen patients received prior pelvic radiotherapy and 3 patients received prior whole abdominal radiotherapy. Nine of the 25 patients had received prior progestational agents, and 2 had received prior systemic chemotherapy. There were no responders, 8 patients had stable disease for a median 5 months (range 1-8), 14 patients progressed on therapy, and 3 patients were not evaluable for response due to receiving only 1 treatment. One patient experienced a grade 3 toxicity that was possibly attributable to Leuprolide (deep venous thrombosis). The median survival from study entry was 6 months. Twelve patients received progesterone after discontinuing this study, and none responded. Leuprolide does not appear to be a clinically active agent in the treatment of recurrent or metastatic endometrial cancer.

Adult↗
PubMed1997

Prediction of obliteration of arteriovenous malformations after radiosurgery: the obliteration prediction index.

OBJECTIVE: To describe the response to single dose photon stereotactic radiosurgery of arteriovenous malformations (AVMs) so that the probability of success or failure of treatment may be predicted for the individual patient. METHOD: The obliteration prediction index (OPI) was calculated for AVMs by dividing the marginal dose of radiation in Gray (Gy) by the lesion diameter in centimetres in cohorts of 42 patients treated with the modified linear accelerator at Toronto-Sunnybrook Regional Cancer Centre and 394 patients treated with the gamma unit at the Royal Hallamshire Hospital, Sheffield, United Kingdom. Patients were grouped into ranges by OPI and the proportion of success and failure was calculated for each group. An exponential function [P = 1-A.e(-B.OPI)] was fitted to the data by the least squares method. RESULTS: Despite systematic differences in radiation treatment, that is, marginal doses of 15 and 20 Gy in Toronto and most Sheffield patients with a marginal dose of 25 Gy, the resultant data points exhibited similar behaviour. CONCLUSION: The function [P = 1-A.e(-B.OPI)] partly describes the biological effect of radiation and is independent of the radiation device used. Radiosurgery centres can use this model to facilitate predictions of successful treatment for individual patients.

Follow-Up Studies↗
PubMed1997

Decreased levels of the cell-cycle inhibitor p27Kip1 protein: prognostic implications in primary breast cancer.

Breast cancer is the second leading cause of cancer death in North American women. There is considerable need for reliable prognostic markers to assist clinicians in making management decisions. Although a variety of factors have been tested, only tumor stage, grade, size, hormone receptor status, and S-phase fraction are used on a routine basis. The cell cycle is governed by a family of cyclin-dependent kinases (cdks), which are regulated by associated cyclins and by phosphorylation. p27Kip1, a cyclin-dependent kinase inhibitor, regulates progression from G1 into S phase by binding and inhibiting cyclin/cdks. p27Kip1 protein levels and/or activity are upregulated by growth inhibitory cytokines including transforming growth factor-beta (TGF-beta) and, thus, provide an important link between extracellular regulators and the cell cycle. Loss of p27Kip1, a negative cell-cycle regulator, may contribute to oncogenesis and tumor progression. However, p27Kip1 mutations in human tumors are extremely rare. We have demonstrated by immunohistochemistry that p27Kip1 protein levels are reduced in primary breast cancers and that this is associated with tumor progression in both in situ and invasive lesions. This was confirmed by western analysis, reflected in increased G1/S-phase cyclin-dependent kinase activities and shown to be regulated posttranscriptionally by in situ hybridization. Furthermore, on multivariate analysis, low p27Kip1 is a predictor of reduced disease-free survival. This simple and reliable immunohistochemical assay may become a routine part of breast cancer evaluation and may influence patient management.

Biomarkers, Tumor↗
PubMed1997

Patterns of motor impairement in normal aging, mild cognitive decline, and early Alzheimer's disease.

In order to determine the relationship between cognitive dysfunction and motor behavior in older adults, 41 cognitively normal elderly (NL), 25 cases exhibiting mild cognitive impairment (MI), and 25 patients with mild Alzheimer's disease (AD) were examined using a broad array to motor/psychomotor and cognitive tests. Relative to the NL group, MI individuals (at risk for future decline to AD) performed worse on tasks involving fine and complex motor function (e.g., tracking and manual dexterity). AD patients also exhibited motor dysfunction on tasks assessing relatively more rudimentary motor control. Motor tasks were able to distinguish NL vs MI and NL vs mild AD individuals as effectively as cognitive tests of memory and language. These results indicate that motor impairment is an important aspect of cognitive decline in older adults. Motor/psychomotor assessments may be comparably sensitive to traditional tests of cognitive function in identifying persons affected by the earliest stages of AD pathology.

Age Factors↗
PubMed1997

Patient preferences for oral versus intravenous palliative chemotherapy.

PURPOSE: To assess patient preference for oral versus intravenous (i.v.) palliative chemotherapy (CT). A strong preference would be an important quality-of-life issue. PATIENTS AND METHODS: A structured interviewer-administered scenario-based questionnaire evaluated incurable cancer patients who would be likely to receive palliative CT in the future. Using probability trade-offs, the preference for route of administration was evaluated against diminishing treatment response. RESULTS: Of 103 assessable patients, 92 preferred oral CT, 10 preferred i.v. CT, and one had no preference. Patient preferences were not associated with age, sex, site of primary cancer, or previous CT experiences. Major reasons for preferring oral CT were convenience, problems with i.v. access or needles, and a better CT-taking environment (outside of the clinic). Regardless of initial preference, 70% of patients were not willing to accept a lower response rate and 74% were not willing to accept a shorter duration of response to retain their initial preference. Although 99% of patients had a preference, 39% wanted the specific treatment decision made primarily by their physicians, 38% primarily by themselves, and 22% shared equally. CONCLUSION: Patients with incurable cancer have a clear preference for oral CT, but are generally not willing to sacrifice efficacy for their preference. Almost 40% of patients did not want to make final treatment decisions themselves.

Administration, Oral↗
PubMed1997

Predicting postlaryngectomy voice outcome in an era of primary tracheoesophageal fistulization: a retrospective evaluation.

OBJECTIVES: Not all laryngectomees appear to have the same potential to develop functional spoken communication. Our goal was to evaluate voice outcome in different functional subgroups of laryngectomees and to identify physical and demographic factors associated with success and failure to achieve functional spoken communication. DESIGN: Retrospective chart review. SETTING: Surgery was performed at a tertiary care hospital. Multidisciplinary follow-up was conducted at weekly head and neck clinics held at the associated regional cancer centre. Voice rehabilitation procedures took place in both settings. PATIENTS: Sixty-four consecutive patients who had undergone total laryngectomy during the era of primary tracheoesophageal fistulization (TEF) at this facility. Patients were subdivided into four groups according to whether they had undergone primary TEF, or whether this had been contraindicated by locoregional factors of TEF candidacy/performance status, or both. INTERVENTIONS: Primary TEF was performed whenever technically feasible and traditional TEF candidacy criteria were met. Voice rehabilitation procedures were initiated prior to discharge. OUTCOME MEASURES: A judgement of voice outcome was assigned based on documentation on at least one of three patient treatment records by a physician or speech-language pathologist that a patient had demonstrated functional spoken communication within the clinical setting. RESULTS: Forty-five of 64 patients (70%) achieved functional spoken communication. Six laryngectomized subgroups were ultimately identified and characterized. Voice outcome varied considerably between these subgroups. Prelaryngectomy communication status and age emerged as predictors of voice outcome. CONCLUSIONS: Voice outcome is related to several factors present prior to or at laryngectomy. Different combinations of such factors create various postlaryngectomy recovery streams for which voice outcome may be predicted more specifically.

Adult↗
PubMed1997

Raynaud's phenomenon and digital gangrene as a consequence of treatment for Kaposi's sarcoma.

OBJECTIVE: To analyze the clinical features and to identify factors associated with the development of Raynaud's phenomenon (RP) in patients receiving chemotherapy for human immunodeficiency virus (HIV) related Kaposi's sarcoma. METHODS: A retrospective cohort study of all patients with Kaposi's sarcoma treated with chemotherapy at Toronto-Sunnybrook Regional Cancer Centre from 1987 to 1995. Patients who developed RP were compared with those who did not with respect to age, CD4 cell count, Acquired Immune Deficiency Syndrome Clinical Trials Group (ACTG) stage, smoking history, type and dose of chemotherapy, and previous treatment with interferon and radiation therapy. RESULTS: Eighty-seven patients with Kaposi's sarcoma were treated with chemotherapy between 1987 and 1995. Five developed RP, which progressed to digital gangrene. Median age, proportion of smokers, proportion defined as ACTG poor risk, median CD4 count, and history of opportunistic infections were equal in the 2 groups. All patients with RP received vinblastine followed by bleomycin. No cases of RP occurred in 27 patients treated with vinblastine alone or in 24 patients treated with bleomycin without previous vinblastine. Patients developing RP tended to have received higher cumulative doses of chemotherapy including bleomycin (p = 0.067) and previous treatment with either local radiation or interferon (p < 0.009, p < 0.001, respectively). CONCLUSION: Sequential chemotherapy with vinblastine followed by bleomycin was associated with the development of RP in patients with HIV related Kaposi's sarcoma. Bleomycin alone was not associated with RP.

Adult↗
PubMed1996

Endometrial carcinoma--relative effectiveness of adjuvant irradiation vs therapy reserved for relapse.

Fifty-four patients with recurrent endometrial carcinoma were identified from a retrospective review of charts of 304 endometrial cancer patients seen between 1983 and 1989 at our center. A review was undertaken to identify the patterns of relapse, to determine the outcome of salvage treatment, to examine the factors predictive of effective salvage, and, if salvage is effective, to assess an alternative strategy to routine adjuvant postoperative pelvic radiotherapy. Forty percent of the entire recurrent population are long-term survivors. Of the 54 relapsing patients, primary therapy had been surgery alone in 32 and surgery and adjuvant radiotherapy (rt) in 22. Isolated pelvic recurrence was the predominate relapse site in those who had not received adjuvant pelvic RT as primary therapy (23 of 32 or 72%). Distant relapse predominated in those who received adjuvant RT (17 or 22 or 77%). Twenty-eight (54%) failed in the pelvis alone, and 26 (46%) had a component of distant failure. Of the 28 with isolated pelvic relapse, 16 had vaginal mucosal disease involvement only and 12 had disease in the parametrium and/or the pelvic sidewall. With a minimum follow-up for the survivors of 5 years, 21 of the 28 with isolated pelvic relapse received radical radiotherapy and 14 or 67% had maintained pelvic control until death or last follow-up. Eleven of 14 (79%) with disease confined to the mucosa had pelvic control, whereas only 3 of 7 (43%) with extramucosal disease were controlled. No patient experienced major treatment-related toxicity. Tumor size, anatomic extent of pelvic recurrence, RT dose, and disease-free interval were examined for prognostic significance for pelvic control and survival by univariate analysis. Only anatomic extent of pelvic recurrence showed a nonstatistically significant trend as a predictor for control with P = 0.08. In conclusion, a significant proportion of patients with disease recurrence confined to the pelvis can be rendered disease-free long-term with maintained pelvic control. A reexamination of the role of routine adjuvant pelvic RT is therefore undertaken in light of these data.

Aged↗
PubMed1996

A menopause-specific quality of life questionnaire: development and psychometric properties.

OBJECTIVE: To develop a condition-specific quality of life questionnaire for the menopause with documented psychometric properties, based on women's experience. METHODS SUBJECTS: Women 2-7 years post-menopause with a uterus and not currently on hormone replacement therapy. Questionnaire development: A list of 106 menopause symptoms was reduced using the importance score method. Replies to the item-reduction questionnaire from 88 women resulted in a 30-item questionnaire with four domains, vasomotor, physical, psychosocial and sexual, and a global quality of life question. Psychometric properties: A separate sample of 20 women was used to determine face validity, and a panel of experts was used to confirm content validity. Reliability, responsiveness and construct validity were determined within the context of a randomized controlled trial. Construct validation involved comparison with the Neugarten and Kraines'Somatic, Psychosomatic and Psychologic subscales, the reported intensity of hot flushes, the General Well-Being Schedule, Channon and Ballinger's Vaginal Symptoms Score and Libido Index, and the Life Satisfaction Index. RESULTS: The face validity score was 4.7 out of a possible 5. Content validity was confirmed. Test-retest reliability measures, using intraclass correlation coefficients were 0.81, 0.79, 0.70 and 0.55 for the physical, psychosocial, sexual domains and the quality of life question. The intraclass correlation coefficient for the vasomotor domain was 0.37 but there is evidence of systematic change. Discriminative construct validity showed correlation coefficients of 0.69 for the physical domain, 0.66 and 0.40 for the vasomotor domain, 0.65 and -0.71 for the psychosocial domain, 0.48 and 0.38 for the sexual domain, and 0.57 for the quality of life question. Evaluative construct validity showed correlation coefficients of 0.60 for the physical domain, 0.28 for the vasomotor domain, 0.55 and -0.54 for the psychosocial domain, 0.54 and 0.32 for the sexual domain, and 0.12 for the quality of life question. Responsiveness scores ranged from 0.78 to 1.34. CONCLUSIONS: The MENQOL (Menopause-Specific Quality of Life) questionnaire is a self-administered instrument which functions well in differentiating between women according to their quality of life and in measuring changes in their quality of life.

Attitude to Health↗
PubMed1996

A comparison of the effects of oral conjugated equine estrogen and transdermal estradiol-17 beta combined with an oral progestin on quality of life in postmenopausal women.

OBJECTIVE: To compare the effect of transdermal estradiol-17 beta and oral conjugated equine estrogen when combined with an oral progestin on quality of life in post-menopausal women. DESIGN: Randomized controlled double-blind trial. A randomization error lead to the exclusion of six subjects but the soundness of the remaining randomization was confirmed. SETTING: Large urban community. PATIENTS: Women 2-7 years after menopause with a uterus and ovaries, and not currently using hormone replacement therapy. Seventy-four women completed the trial. INTERVENTIONS: After baseline measures of quality of life, subjects were randomly assigned to either continuous oral conjugated equine estrogen 0.625 mg daily or continuous transdermal estradiol-17 beta 50 mcg twice weekly, for four 4-week cycles. Medroxyprogesterone acetate 10 mg oral tablets was administered to both groups for the last 12 days of each cycle. OUTCOMES MEASURED: Quality of life was determined using the Menopause-Specific Quality of Life Questionnaire. Tolerability was determined by a specifically designed list of adverse effects. Both measures were recorded at base-line and in mid-cycle during the second, third and fourth cycles of treatment. RESULTS: There were no statistically significant differences in any of the domains at baseline between the oral and transdermal treatment groups. In the vasomotor domain-scores for the oral and transdermal groups improved from baseline levels of 3.14 and 3.09, respectively, to 1.32 and 1.23; physical domain scores improved from 2.45 and 2.73 to 2.04 and 1.78; psychosocial domain scores improved from 2.72 and 3.04 to 2.21 and 1.94; sexual domain scores improved from 2.32 and 2.16 to 1.64 and 1.30. There were no statistically significant group differences or time/group interactions. Both forms of therapy were equally well tolerated. CONCLUSIONS: Improvement in all domains, measured by the Menopause-Specific Quality of Life Questionnaire, was observed in both the oral and transdermal groups. In the absence of a placebo control group, the improvements observed cannot be attributed solely to the therapy. Neither form of therapy offered an advantage over the other in respect to improvement in quality of life.

Administration, Cutaneous↗
PubMed1995

Free forearm flap in oral reconstruction. Functional outcome.

OBJECTIVE: To examine functional outcome associated with free radical forearm flap reconstruction of oral cavity and oropharyngeal defects. DESIGN AND SETTING: Case series obtained from a head and neck clinic conducted at a regional cancer center. Patients underwent surgery at the associated tertiary care center. PATIENTS: Thirty consecutive patients treated for oral and oropharyngeal malignant neoplasms staged from T1 to T4 were studied. Subjects were assigned to five groups based on the site and extent of their surgical resections, as specified on a resection template. INTERVENTION: All patients had undergone free radial forearm flap reconstruction of their surgical defects. OUTCOME MEASURES: Ten factors reflecting functional properties and processes of the upper aerodigestive tract were evaluated clinically or with videofluoroscopy or both. RESULTS: Near-normal and fair oral and oropharyngeal function wholly characterized the sample. Patients who underwent reconstruction of unilateral tongue, floor of mouth-ventral tongue, and retromolar trigone-buccal defects functioned well on most measures; the function of patients with anterior tongue-jaw and tongue base-tonsil defects varied. CONCLUSIONS: Functional outcome with free radial forearm flap reconstruction was favorable for three of five subgroups of oral and oropharyngeal cancer patients. Qualitatively different functional profiles emerged for subgroups based on resection site. Methodologic issues for research on surgical reconstruction and functional outcome include the need for a meaningful, reliable system of classifying oral and oropharyngeal resections, and the development of standardized procedures for evaluating functional outcome.

Adult↗
PubMed1995

Does aggressive therapy improve survival in suboptimal stage IIIc/IV ovarian cancer? A Canadian-American comparative study.

In an effort to determine if differences exist in the treatment and outcome of patients with suboptimally debulked stage IIIc and IV epithelial ovarian cancer between two tertiary-care cancer centers in Canada and the United States, we conducted a comparative study. The records of all patients who underwent treatment for epithelial ovarian cancer at two tertiary-care cancer centers in Canada and the United States between 1987 and 1989 were abstracted onto a common datasheet which was then entered into a computerized database for analysis. Only patients with suboptimally debulked stage IIIc disease (residual tumor diameter > 1 cm) or stage IV were included in the comparative study. There was a total of 129 evaluable patients (61 Canadian, 68 American). There were no statistically significant differences between the centers in mean age, performance status, histology, grade, or stage distribution. During the period of this study there was no statistically significant difference between the two institutions in the proportion of patients in whom optimal debulking was achieved (Canadian 19%, American 26%). The American patients were heavier than the Canadian patients (Quetelet index 27.3 vs 23.8, P < 0.006). Primary chemotherapy included a platin-containing regimen in 98 and 93% of Canadian and American patients, respectively. The average number of laparotomies each patient received during her course of illness was 1.7 and 2.5 at the Canadian and the American centers, respectively (P < 0.0001). Similarly, the American patients received a higher mean number of different chemotherapy regimens and total number of courses of chemotherapy during the course of their disease (3.0 and 12.6) than did the Canadian patients (2.4 and 8.8) (P < 0.01 and P < 0.001, respectively). The median survival was 21 months and 20 months in the Canadian and the American patients, respectively (no significant difference), and the 5-year survival was 10% for the Canadian and 11% for the American patients. Despite significant differences in the overall aggressiveness of treatment between the two centers, there was no difference in the survival of these patients. Until effective salvage agents or treatment strategies are realized, "more is not necessarily better."

Actuarial Analysis↗
PubMed1995

Meta-analysis comparing cisplatin total dose intensity and survival.

OBJECTIVE: To determine the relationship between total dose intensity (TDI) of cisplatin/carboplatin, total dose intensity of all chemotherapy drugs (GDI) and median survival (MS) in stage III-IV ovarian cancer patients. METHODS: Over 700 studies from the English literature were reviewed. Prospective clinical trials that had at least one arm treating patients with cisplatin/carboplatin and provided data on both MS and dose and schedule of chemotherapy were included. Dose intensity (DI), TDI, and GDI were calculated for each study arm. To explore possible relationships, several linear regression models were fitted with MS as the dependent variable and DI, TDI, GDI, and other known prognostic factors as the independent variables. RESULTS: Sixty-one study arms were analyzed including 4118 patients. No significant correlation was found between DI and TDI of cisplatin and MS (P = 0.90 and P = 0.11 respectively). Of the 10 variables tested, proportion of patients optimally debulked (%OD), proportion of mucinous tumor, and GDI were found to have a significant correlation to MS. All studies with a GDI less than 20 and %OD < 20 had a MS less than 20 months. On the other hand 77% of studies have a MS greater than 20 months when GDI is > 20 and %OD > 20%. We found single-agent chemotherapy had the worst outcome and there was very little difference between two or more drugs for percentage of studies with > 20 months MS, (56.5% vs 63.3% respectively). CONCLUSIONS: From this meta-analysis we believe that both GDI and %OD are important factors that determine outcome in terms of median survival.

Antineoplastic Agents↗
PubMed1994

Significance of a partial or slow response to front-line chemotherapy in the management of intermediate-grade or high-grade non-Hodgkin's lymphoma: a literature review.

PURPOSE: The purpose of this review was to assess the outcome of patients with non-Hodgkin's lymphoma (NHL) who achieve an incomplete or slow response to front-line chemotherapy and to determine whether salvage treatment with intensive combination chemotherapy with or without autologous bone marrow transplantation (ABMT) is successful in such patients. METHODS: A comprehensive literature search of studies using combination chemotherapy for the front-line therapy of advanced-stage intermediate- and high-grade NHL and for salvage therapy of patients with a partial response (PR) was reviewed. RESULTS: The median survival duration of patients with a PR ranged between 5 to 14 months, while the median survival duration of patients with a complete response (CR) was not reached in many studies. For patients in CR, the probability of survival at 24 months ranged between 0.79 to 1, while for patients in PR it ranged from 0 to 0.31. The rapidity of a response to front-line therapy was often found to be of prognostic importance. Patients who relapsed after a PR to front-line therapy had similar outcomes to intensive salvage therapy as those who relapsed after a CR. ABMT performed immediately after a PR to induction therapy, before progressive disease occurred, resulted in high CR rates in nonrandomized studies. CONCLUSION: Patients with aggressive NHL who experience a PR or who respond slowly to front-line chemotherapy have a poor prognosis. Early introduction of dose-intensive salvage therapy before the development of progressive disease may benefit patients with a PR and requires testing in randomized clinical trials.

Antineoplastic Combined Chemotherapy Protocols↗