Ondansetron in a patient with porphyria.
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Antineoplastic Agents↗
Biomedical subjects
G Falkson
Publications and source records attributed to G Falkson.
[Intraperitoneal recombinant gamma interferon (RU 42369) efficacy in ovarian carcinomas. European BRM Study Group].
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Adenocarcinoma↗
Chemotherapy versus observation in high-risk node-negative breast cancer patients.
Postoperative women with breast cancer but without histopathological evidence of metastases to the axillary lymph nodes or clinical evidence of metastases were studied. Six hundred fifty-five "good-risk" patients who were estrogen receptor positive (ER+) with primary tumors less than 3 cm were registered for observation. Twenty-four of these patients were treated with chemotherapy. Five hundred thirty-six "poor-risk" patients who were either ER+ with primary tumors greater than or equal to 3 cm or estrogen receptor negative (ER-) with any primary tumor size were randomly assigned between chemotherapy and observation. Randomization was stratified by type of surgical procedure, number of lymph nodes examined, menopausal status, tumor size, and ER status. The chemotherapy (CMFP) consisted of six 4-week cycles of cyclophosphamide, 100 mg/m2 orally days 1-14; methotrexate, 40 mg/m2 intravenously (IV) days 1 and 8; fluorouracil, 600 mg/m2 IV days 1 and 8; and prednisone, 40 mg/m2 orally days 1-14. Treatment arms in the randomly assigned patients were balanced with respect to pretreatment characteristics. This analysis includes 445 eligible patients entered in the registration arm and 425 eligible patients entered into the randomized treatments. The median follow-up is 4.5 years in the randomly assigned cohort and 4.8 years in the registered cohort. The overall 5-year disease-free survival (DFS) among the randomly assigned patients was 83% with CMFP and 61% with observation (P less than .0001). A DFS treatment benefit was observed in premenopausal and postmenopausal patients as well as in patients with ER+ or ER- tumors. There were fewer local-regional and distant relapses among the CMFP-treated patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Metastatic breast cancer--age has a significant effect on survival.
The data on 217 elderly (aged greater than or equal to 65 years) and 209 middle-aged postmenopausal patients with metastatic breast cancer treated in the Department of Medical Oncology, University of Pretoria, from 1976 to 1985 were analysed to determine the effect of age on survival. When considered as a group, the elderly have a more favourable prognosis (median survival 20.3 months) than the middle-aged (median survival 15.54 months) (P = 0.0457). Multivariate age subset analysis (taking into account all other major prognostic factors) reveal a distinct bimodal pattern. The median survival of patients aged 45-54 years is 21.2 months and decreases to 16.2 months for patients aged 55-64 years (P = 0.08; Cox model). The median survival improves again to 24.6 months for patients aged 64-74 years (P = 0.0001; Cox model), followed by an apparent but non-significant decrease to 17.1 months in the very old (aged 75-84 years) (P = 0.52; Cox model). The more favourable prognosis in the elderly dictates effective non-toxic treatment.
Age Factors↗
Prognostic factors affecting the survival of patients with multiple myeloma. A retrospective analysis of 86 patients.
A retrospective analysis of data concerning 86 patients with multiple myeloma was carried out in order to evaluate factors affecting survival. The overall median survival was 621 days. In a univariate analysis the following factors were significantly associated with poor survival: serum creatinine greater than or equal to 150 mmol/l, haemoglobin less than 11 g/dl and serum calcium values greater than 2.75 mmol/l; and Eastern Cooperative Oncology Group performance status 3-4. However, age, sex, Durie and Salmon staging, lytic lesions, serum immunoglobulin concentration, urine Bence Jones protein, percentage of plasma cells in the bone marrow, proteinuria, and type of chemotherapy given were not significantly associated with survival. A strong prediction of survival was found by grouping the serum creatinine and haemoglobin levels of patients at presentation.
Adult↗
Trisomy 5 in Ph+ chronic myeloid leukemia in association with megakaryocytosis.
A patient with a megakaryocytosis associated with a Philadelphia chromosome-positive chronic myeloid leukemia (CML) was found to have a trisomy of chromosome five. To our knowledge, this is the first case of trisomy 5 associated with a Ph + CML, particularly one with a megakaryocytosis. The trisomy 5 may be associated with the resistance to cytostatic drugs found in this patient.
Chromosomes, Human, Pair 5↗
Effect of chemotherapy with or without buserelin on serum hormone levels in premenopausal women with breast cancer.
Serial determinations of serum oestradiol (E2), follicle-stimulating hormone (FSH) and luteinising hormone (LH) were done to assess the effect of chemotherapy, with or without a gonadotropin-releasing hormone analogue, buserelin, on ovarian function in 147 premenopausal women treated for breast cancer. Cyclophosphamide, doxorubicin and 5-fluorouracil (CAF) plus buserelin was given to 81 women with metastatic disease, and 66 women were randomised to adjuvant cyclophosphamide, methotrexate and 5-fluorouracil (CMF) with buserelin or CMF alone. Baseline mean E2 of patients treated with cytostatics plus buserelin fell from premenopausal levels and remained low while patients were on study. E2 levels remained at premenopausal values in patients treated with CMF alone. Downregulation of FSH and LH occurred with cytostatics plus depot buserelin, but fluctuated with the nasal administration; on CMF alone, FSH and LH levels increased. Buserelin plus cytostatics more effectively caused ovarian ablation than cytostatic treatment alone. Depot buserelin was more effective than nasal buserelin.
Adult↗
Long-term survival of patients treated with combination chemotherapy for metastatic breast cancer.
Long-term survival of patients with metastatic breast cancer treated on two prospective stratified randomised trials has been analysed. Patients on study B122 received either cyclophosphamide, methotrexate and 5-fluorouracil (CMF) or cyclophosphamide, doxorubicin and 5-fluorouracil (CAF). On study B141 patients received CAF or mitolactol (dibromodulcitol), doxorubicin and vincristine alternating after every three cycles with three cycles of CMF (DAV/CMF). Long-term follow-up of 172 patients showed no significant survival difference (in multivariate regression models) for treatment with either CMF vs. CAF or CAF vs. DAV/CMF. The difference in median survival times between CMF and CAF showed a trend in favour of CAF. Advances in the management of metastatic breast cancer in postmenopausal women obtained by doxorubicin regimens have had a small but measurable impact on survival, but known patient discriminants were not overridden by the treatment regimens investigated in these studies.
Antineoplastic Combined Chemotherapy Protocols↗
Long term follow-up of patients with advanced prostatic cancer treated with nasal buserelin.
Sixty one men, with advanced prostatic cancer, were entered on a trial using a nasally administered gonadotropin-releasing hormone analogue agonist, buserelin, as first line treatment. This is the first trial to use intranasal buserelin without primary injections and without antiandrogens. No 'flare' phenomenon was observed. The only side effects were hot flashes (69%) and decreased libido (25%). The response rate of 82%, with a median response duration of 16 months, compares favourably to responses reported with orchidectomy or estrogens. Serum testosterone, FSH and LH were monitored at regular intervals. Mean serum testosterone baseline values of 15 nmol/L decreased to castrate levels, and remained low while patients were on study. It is concluded that intranasal buserelin is an effective, simple and safe method to achieve androgen deprivation and is an alternative to orchidectomy in the treatment of advanced prostatic cancer.
Administration, Intranasal↗
Phase II study of aminothiadiazole in advanced squamous cell carcinoma of the esophagus.
Twenty-three patients with advanced inoperable squamous cell carcinoma of the esophagus were treated with aminothiadiazole (A-TD) 125 mg/m2 weekly plus allopurinol daily in a phase II cooperative group trial. No patients responded to treatment; 17 patients progressed, three showed stable disease, and three were unevaluable. There were no life-threatening hematologic or metabolic toxicities. The median survival from study entry was 5 months. A-TD is not active in advanced squamous cell carcinoma of the esophagus.
Adult↗
A pilot study of three sequential chemotherapeutic regimens in metastatic breast cancer.
The aim of this pilot study was to estimate the toxicity and response rate of an alternating chemotherapeutic program in chemotherapy-naive metastatic breast cancer patients. Treatment consisted of regimen A (given days 1-28): cyclophosphamide 100 mg/m2 PO days 1-14, doxorubicin 30 mg/m2 i.v. days 1 and 8, and 5-fluorouracil 500 mg/m2 i.v. days 1 and 8 (CAF regimen); regimen B (given days 29-56): dibromodulcitol 135 mg/m2 p.o. days 30-39, mitoxantrone 9 mg/m2 i.v. day 29, and vincristine 1.2 mg/m2 i.v. (maximum 2.0 mg) day 29 (DMV regimen); and regimen C (given days 57-84): thiotepa 12 mg/m2, doxorubicin 45 mg/m2 and vinblastine 4.5 mg/m2 all i.v. on day 57. There were 27 eligible patients with a median age of 51 years (range 34-78). On 14 episodes the leukocyte count fell to less than 1 X 10(9)/L during the first six cycles of treatment (14% of 99 cycles). There were no treatment-related deaths. Common non-life-threatening toxicities included thrombocytopenia, anemia, vomiting, and alopecia. Despite having no drugs in common, the leukocyte and platelet nadirs after CAF correlated with the nadir counts after DMV (r values of 0.6829 and 0.5892, respectively; p = 0.01). Among the 23 patients with measurable and/or evaluable disease there were five complete responses (22%) and nine partial responses (39%), with a median time to treatment failure of 29 weeks. The overall median survival was 19 months.
Adult↗
Sister chromatid exchanges in lymphocyte cultures of patients previously treated with dibromodulcitol.
Acute non-lymphatic leukaemia and myelodysplasia occur in a larger percentage of patients treated with dibromodulcitol (DBD) than in patients treated with other cytostatics. Sister chromatid exchanges (SCE) in the lymphocytes in peripheral blood as well as other haematological parameters were measured in women with breast cancer to investigate whether women who had previously been treated with DBD as a part of their treatment regime had an increased frequency of SCE or another haematological abnormality attributable to DBD. SCE levels were elevated in women treated with DBD as well as in those treated with other cytostatics compared to the untreated control group. All other haematological parameters were normal. There was no significant difference in the number of SCEs between the patients who received DBD and those treated with other cytostatics. The increased frequencies of SCE in the treated patients are attributable to various cytostatic agents, and there is no significant permanent increase in the frequency of SCE after exposure to DBD.
Breast Neoplasms↗
Cisplatin, carboplatin, and cyclophosphamide combination chemotherapy in advanced-stage ovarian carcinoma: an Eastern Cooperative Oncology Group pilot study.
Cyclophosphamide (CTX) 600 mg/m2, carboplatin 280 mg/m2, and cisplatin 50 mg/m2 were administered on day 1 every 4 weeks to 41 previously untreated ovarian cancer patients with residual disease greater than 2.0 cm after primary laparotomy. Of 22 patients with measurable disease treated with up to eight cycles of therapy, the overall clinical response rate was 73% (exact 95% confidence interval [CI], 50% to 89%), with 50% complete response (CR). Six of 11 clinical CR (cCR) patients underwent surgical restaging; three pathologic CRs (pCRs) and three pathologic partial responses (pPRs) with residual disease less than 2.0 cm were documented. Fourteen patients had nonmeasurable but assessable disease; the clinical response rate was 57% (Cl, 29% to 82%) with two (14%) CRs. Second-look surgery was performed in one of the two cCR patients; a pPR was documented. Five patients with nonassessable disease were stable during chemotherapy; two underwent surgery and had pCRs. The median time to treatment failure (TTF) was 14.8 months, and median survival for the 41 patients is 26.7 months. Overall, 37% of the patients had progression-free intervals of at least 2 years, and 27% have survival times in excess of 3 years. Hematologic toxicity was substantial but manageable, with 58% and 66% experiencing a granulocyte nadir less than 500/microL and a platelet nadir less than 50,000/microL, respectively. One treatment-associated fatality occurred as a result of leukopenic sepsis and renal failure in the setting of progressive disease and ureteral obstruction. Mild to moderate nausea and vomiting occurred in most patients, but none experienced severe ototoxicity or peripheral neuropathy. Over all courses, 73% of the projected dose intensity of CTX and carboplatin and 86% of cisplatin were delivered. Since granulocytopenia and thrombocytopenia were dose-limiting, the addition of colony-stimulating factors that support both myeloid and megakaryocyte precursors may permit further dose intensification.
Adenocarcinoma↗
Factors predicting for response, time to treatment failure, and survival in women with metastatic breast cancer treated with DAVTH: a prospective Eastern Cooperative Oncology Group study.
Six hundred twenty-four women with metastatic breast cancer were entered on Eastern Cooperative Oncology Group (ECOG) study EST 2181. Patients were treated with mitolactol, doxorubicin, vincristine (DAV), tamoxifen, and fluoxymesterone (DAVTH). Nine patients were canceled, and 114 were ineligible (half because of concomitant diseases). Among the 501 eligible patients, the overall response rate was 54% (14% complete response and 5% not assessable). The median time to treatment failure (TTF) was 9.0 months, and the median survival was 20.9 months. Multivariate models were fit on a randomly chosen half of the eligible cases and then verified on the other half. About half of the variables that were significant in the models remained significant in the verification data set. In the verification data set the variables that remained significantly associated with lower probability of response were three or more organ sites of disease and lack of nodal metastases; the variables associated with a significantly shorter TTF were liver metastases, estrogen receptor (ER)-negativity, and prior adjuvant therapy. The variables associated with significantly shorter survival were liver metastases, ER negativity, three or more organ sites of disease, and prior adjuvant chemotherapy. None of the variables in the data set had a significant influence on toxicity. The 125 patients aged over 65 years did not have worse toxicity or worse prognosis than younger patients. Ineligible patients had significantly less response but virtually identical TTF curves, survival curves, and toxicities. Therefore, patient discriminants are of paramount importance in predicting the outcome of treatment. Many of the current criteria for eligibility for entry on study may not be justified.
Adenocarcinoma↗
Improved results with the addition of interferon alfa-2b to dacarbazine in the treatment of patients with metastatic malignant melanoma.
Sixty-four patients with histologically confirmed metastatic malignant melanoma were entered on a prospectively controlled randomized trial. Patients received dacarbazine (DTIC) alone or DTIC plus interferon (IFN) alfa-2b. Patients were reasonably balanced with respect to age, sex, performance status (PS), site of metastases, and number of metastatic sites. Objective response (complete plus partial remission [CR + PR]) was documented in six patients on DTIC and in 16 patients on DTIC plus IFN alfa-2b. Median time to treatment failure (TTF) and median survival are significantly better on the combination arm, with some long-term CRs observed. More toxicity was encountered in the combination arm, which was acceptable except in three patients where treatment was discontinued because of IFN toxicity.
Adult↗
Factors influencing prognosis in elderly patients with primary breast cancer.
A retrospective analysis was performed on 260 elderly and 294 middle-aged patients with primary breast cancer. Cox regression analysis showed that the classic prognostic factors, such as negative lymph node status, small tumour size and positive oestrogen receptor (ER) status, were favourable indicators of survival and were similar in both the elderly and the middle-aged. When the elderly and middle-aged were considered together, older age (favourable) and the presence of association disease (detrimental) were additional significant prognostic factors. It is concluded that a physically fit elderly woman in the present study had a more favourable survival outlook than a younger counterpart with similar tumor size, lymph node and ER status and should be given the best available treatment based on tumour characteristics and not on age alone.
Age Factors↗
A phase II study of idarubicin and prednisone in multiple myeloma.
Twenty-one patients with multiple myeloma were treated with idarubicin 45 mg/m2 orally day 1 and prednisone 60 mg/m2 day 1-4 every three weeks. Moderate to severe gastrointestinal and hematopoietic toxicity were observed. Twelve of the twenty-one patients had relapsed on prior treatment. Of these, 2 patients responded. Two patients had primary resistant disease, neither responded. Seven patients had received no prior treatment, three responded. Idarubicin and prednisone have modest activity in refractory myeloma, with short duration of response and severe toxicity.
Antineoplastic Combined Chemotherapy Protocols↗
Survival of premenopausal women with metastatic breast cancer. Long-term follow-up of Eastern Cooperative Group and Cancer and Leukemia Group B studies.
In premenopausal women with metastatic breast cancer, differences in survival curves early during follow-up can be misleading. The authors therefore analyzed long-term survival in 378 patients, entered in three randomized trials, started between 1973 and 1978. Combined data from the three trials were used to increase the power for identifying prognostic variables. Cancer and Leukemia Group B (CALGB) trial 7382 randomized patients to oophorectomy plus either cyclophosphamide or combination chemotherapy or observation. Eastern Cooperative Oncology Group (ECOG) 2174 randomized patients who had not progressed 3 months after oophorectomy to combination chemotherapy or combination chemotherapy or observation. Trial ECOG 2177 randomized estrogen receptor (ER) positive or ER-unknown patients to oophorectomy plus combination chemotherapy or immediate combination chemotherapy, and ER-negative patients were directly assigned to combination chemotherapy. Hence ER-negative patients need not have been healthy enough to be randomized to oophorectomy. With only 14% of the patients still alive, median survival on the three studies was 30, 24, and 28 months. The median survival of individual treatments changed noticeably in ECOG 2174 and ECOG 2177 with long-term follow-up. At this time there are no differences in survival between randomized regimens in any of the three trials. In a multivariate model, factors associated with significantly poorer survival were visceral-dominant disease, nodal metastases, breast metastases, age younger than 45 years, ER negativity, and not receiving chemotherapy immediately after oophorectomy. This treatment difference was thus not due to imbalances in the prognostic variables used in the model, but it may be due to imbalances of unknown prognostic factors or differences in patient selection.
Adult↗