Adjuvant and palliative treatments of colon cancer.
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Antineoplastic Combined Chemotherapy Protocols↗
Biomedical subjects
P Alberto
Publications and source records attributed to P Alberto.
Feasibility of quality of life assessment in a randomized phase III trial of small cell lung cancer--a lesson from the real world--the Swiss Group for Clinical Cancer Research SAKK.
Between 1985 and 1990 the Swiss Group for Clinical Cancer Research (SAKK) for the first time assessed quality of life (QL) variables in 188 patients in a multicenter small-cell lung cancer trial that compared two different regimens of combination chemotherapy. QL-assessment was scheduled at the beginning of each of the six treatment cycles. The self-rating QL questionnaire included an early version of the EORTC QL questionnaire, a mood adjective checklist (Bf-S) and a single linear analogue scale (LASA) measuring general well-being. Compliance with completion of the scheduled questionnaires varied between 37% and 58% over the six cycles, and between 21% and 68% among the 7 participating institutions. Mean compliance was 49%. The institution was found the only significant factor predicting compliance (p < 0.001). Patient age, sex, education and biological prognostic factors at randomization were not predictors of compliance. Although compliance was poor, the data received was of high quality. We suggest practical guidelines for improving compliance with QL data collection in multicenter clinical trials.
Antineoplastic Combined Chemotherapy Protocols↗
Results of the first ESMO examination in medical oncology, London 1989.
Since 1989, a Certification in Medical Oncology is offered to ESMO members on the basis of their professional curriculum vitae and of their scores in a multiple choice examination. The first session took place in London, U.K., in September 1989, during ECCO 5. One hundred and twenty-five ESMO members were evaluated by means of 60 multiple choice questions covering various aspects of medical oncology, such as tumor diagnosis, prognosis and treatment, drug pharmacology and toxicity, histology and cytology, epidemiology, carcinogenesis and tumor biology. The mean percent of correct answers was 77.4. The best results were obtained with questions dealing with chemotherapy. Scores of 40% or less were obtained in 8 questions, including 2 questions on AIDS related tumors. A similar examination is available in 1990 and will be prepared yearly in the future. It is hoped that this European ESMO Certification will contribute to lessen the professional discrepancies between oncologists of European countries and improve the level of oncological training in Europe.
Certification↗
Antiemetic efficacy of droperidol or metoclopramide combined with dexamethasone and diphenhydramine. Randomized open parallel study.
We have performed an open parallel randomized study of the efficacy of two antiemetic drug combinations. Dexamethasone (10 mg i.v.), diphenhydramine (25 mg i.v.), and metoclopramide (3 mg/kg, 15 min i.v.) or droperidol (1.25 mg slow push) were given 30 min before and 90 min after start of chemotherapy. Thirty-six patients treated with cisplatin-based regimens (30 mg/m2 x 3 days or 60 mg/m2 day 1 only), have been observed for 48 h after their last chemotherapy. Twelve (67%, confidence interval 95%: 41-87%) experienced no vomiting while on metoclopramide and 11 (61%, confidence interval 36-83%) were protected by droperidol. Further patient accrual was stopped because of side effects in one study arm. Moderate sedation (difficulty to keep up a conversation) was observed in 48% of those on metoclopramide versus 14% of those on droperidol (p less than 0.05). We conclude that low-dose droperidol combinations can offer antiemetic protection for patients treated with moderate-dose cisplatin-based chemotherapies. In view of the potential for severe long-term neurologic problems due to metoclopramide or droperidol, these and similar drugs should be used at the lowest possible dose.
Adolescent↗
Combination chemotherapy with mitomycin, vindesine, and cisplatin for non-small cell lung cancer. Association of antitumor activity with initial tumor burden and treatment center.
From 1984 through 1986, 205 patients with non-small cell lung cancer were entered into a group-wide trial of the Swiss Group for Clinical Cancer Research (SAKK). This trial evaluated the combination of mitomycin (8 mg/m2 intravenously [IV] on day 1), vindesine (3 mg/m2 IV on days 1 and 8), and cisplatin (60 mg/m2 IV on day 1) with forced diuresis, repeated every 4 weeks (MiViP regimen). One hundred eighty-three patients were evaluable. Six complete and 69 partial responses were documented for an overall response rate of 41% (95% confidence interval, 34% to 50%). In the multivariate analysis the strongest predictors for response were the participating institution and the number of initially involved organ sites. The estimated median time to progression for patients with a complete response, partial response, or stable disease was 155 days (estimated inter-quartile range, 99 to 258 days). In the multivariate analysis the time to progression was significantly associated with the number of involved organ sites (P = 0.041). The estimated median survival time for the 183 evaluable patients was 239 days (estimated inter-quartile range, 137 to 436 days). In univariate and multivariate analyses performance status, number of involved organ sites, pretreatment status with radiation therapy, and participating institution were all significantly associated with survival. The principal toxicities were myelosuppression and nausea and vomiting with 16% of the patients refusing further treatment after a median of four cycles of chemotherapy. In conclusion, the MiViP regimen was an active combination chemotherapy in patients with non-small cell lung cancer in a large trial performed by the SAKK. The prognostic value of the participating institution and the number of organ sites involved by metastatic deposits in non-small cell lung cancer needs further investigation.
Adult↗
Tumor necrosis factor/cachectin and lymphotoxin gene expression in lymph nodes from lymphoma patients.
We investigated the mRNA content for tumor necrosis factor (TNF)/cachectin and lymphotoxin (LT) in tumoral tissues of a prospective series of 35 non-Hodgkin's (NHL) and 23 Hodgkin's (HL) lymphomas, to assess their postulated contribution to systemic symptoms. Total RNAs were extracted from diagnostic tissue specimens and submitted to Northern blot analysis, using specific TNF and LT cRNA probes. High amounts of TNF mRNA were found exclusively in NHL (12/35). The majority (9/12) of these were low grade B-cell NHL, which contained a uniform population of malignant cells. In contrast, abundant LT mRNA production was detected in most HL (21/23) and in 19 of 35 NHL. The highest LT mRNA levels were observed in high grade NHL and in lymphocytic predominant subtypes of HL specimens. A significant correlation was found between TNF/cachectin and LT gene expression in NHL and the presence of constitutional symptoms. The biologic and prognostic implications of these preliminary findings are presently unknown, but they demonstrate that lymphoma tissues sharing common histologic features are highly heterogeneous in their ability to synthesize cytokines susceptible to playing a role in the growth control of malignant cells. These results suggest that the evaluation of TNF/cachectin and LT production in lymphomas may help to elucidate the mechanisms of tumoral fever and cachexia.
Blotting, Northern↗
[Doxifluridine toxicity, a fluorouracil analog with low myelosuppressive effect].
Doxifluridine, a new fluorouracil analog with a low myelosuppressive effect, has recently been subject to various disease-oriented, Phase II trials. For the present evaluation of drug tolerance, the Phase II data of 114 patients having received 376 doxifluridine cycles has been used. The treatment cycles consisted of 5 daily intravenous injections of 4,000 mg/m2 non-pretreated patients, and 3,000 mg/m2 in pretreated patients. Previous observations showing that doxifluridine is less myelotoxic than fluorouracil have been confirmed. 54% of the patients had no leucopenia (maintaining WBC counts over 3,000/mm3 and 90% had no thrombopenia (platelets not lower than 100,000/mm3) throughout treatment. However, a WHO grade 4 hematologic toxicity was observed in 9 patients, and 2 toxic deaths were related to severe granulocytopenia and sepsis. Digestive tract toxicity was similar and equally frequent as the one observed with fluorouracil: mucositis with oral ulcerations (19%), nausea and vomiting requiring specific treatment (8%) and severe but never hemorrhagic diarrhoea (5%). Neurologic toxicity was frequent, with 20% of patients complaining of somnolence and/or peripheral neuropathy, 7% of impaired consciousness and 1% of WHO grade 4 cerebellar ataxia. Among the 10% of patients with cardiac symptoms, 6% were benign and transient arrhythmias, and 4% were severe, including 1 myocardial infarction, 1 spontaneously reversible cardiac arrest and 2 ventricular fibrillations successfully treated with cardioversion. In spite of its encouraging antitumor activity and its good hematologic tolerance, intravenous doxifluridine, as used in this study, cannot be recommended because of the observed neurologic and cardiac toxicity. Oral doxifluridine is presently under investigation with preliminary results suggesting a lack of neuro- or cardiotoxicity.
Administration, Oral↗
[Simultaneous bilateral forms of breast cancer].
Faced with three cases of bilateral simultaneous breast cancer over a short period of time, we asked ourselves whether we were dealing with a specific anatomo-clinical entity, what is the prognosis, and what should be the best therapeutic approach. The medical literature is characterized by a small number of papers devoted specifically to this topic and no possible comparison among these papers, because of their differences in the definition of bilateral simultaneous breast cancer. However, our review of the literature led us to think that bilateral simultaneous breast cancer is not a specific entity, and also that the presence of a contralateral simultaneous breast cancer does not worsen the prognosis. Therefore, the treatment should not be different from the treatment of a unilateral breast cancer.
Breast↗
Phase I study of oral doxifluridine using two schedules.
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Adult↗
[Adjuvant treatment].
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Antineoplastic Combined Chemotherapy Protocols↗
A randomized comparison of doxifluridine and fluorouracil in colorectal carcinoma.
In a randomized study 52 patients with advanced colorectal cancer and measurable lesions were treated with doxifluridine 4000 mg/m2 or fluorouracil 450 mg/m2 i.v. on 5 consecutive days over 3 weeks. None had prior fluoropyrimidines except two who received adjuvant fluorouracil. Partial responses with a duration ranging from 259 to 406 days were observed in five patients treated with doxifluridine and two patients treated with fluorouracil. Toxic reactions were evaluated in 88 doxifluridine courses and 105 fluorouracil courses. The most frequent adverse effects were neurotoxicity (48% of patients) and mucositis (43%) for doxifluridine, leukopenia (48%) and nausea/emesis (37%) for fluorouracil. Mucositis, diarrhea, nausea, emesis and skin reactions were observed in both treatment groups. Fluorouracil produced neurotoxic effects in 26% of patients. Reversible cardiac dysfunctions were observed in four patients treated with doxifluridine, expressed by ectopic ventricular beats (2) precordial pains (1) and ventricular fibrillation (1). This latter toxicity justified the premature interruption of the study. Doxifluridine is an active agent in colorectal cancer. Compared to fluorouracil it produces, when used i.v., a lower myelosuppression and a greater incidence of neurological and cardiac toxicity.
Adenocarcinoma↗
A phase II study of doxifluridine in patients with advanced breast cancer.
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Adult↗
Surgery as part of a combined modality approach for inflammatory breast carcinoma.
From November 1977 to February 1984 21 patients with inflammatory breast carcinoma (IBC) were treated in a prospective, nonrandomized study with initial chemotherapy, consisting of a combination of chlorambucil, methotrexate, 5-fluorouracil, and doxorubicin. Modified radical mastectomy was performed after three courses of chemotherapy followed by another six courses of the same chemotherapy. Locoregional radiotherapy concluded the treatment program. All patients responded clinically to the initial chemotherapy. Modified radical mastectomy provided a direct histologic control of the effectiveness of the treatment and, in case of tumor persistence, allowed cytoreduction. No scarring problems were observed and postoperative chemotherapy could be administered without any delay. Radiotherapy was decisive for locoregional tumor control which was obtained in all patients who were treated strictly according to the protocol. Dermal lymphatic involvement represented in this series of clinical inflammatory breast carcinoma no pejorative feature and positive hormone receptors failed to be of predictive value for response to treatment. Considerably variable tumor persistence after initial chemotherapy and the results relative to local tumor control advocate surgery as part of a combined modality approach for inflammatory breast carcinoma.
Antineoplastic Combined Chemotherapy Protocols↗
Long-term results of two Swiss AML studies.
The Swiss group for clinical cancer research (SAKK) completed two first line protocols for the treatment of acute myelogenous leukemia (AML). In the first protocol (SAKK AML 74, from August 1974 to April 1977; 107 patients) the effectiveness of immunization with viral oncolysate during maintenance treatment was tested. After successful induction treatment, the patients were randomized in two groups: Group A: monthly maintenance chemotherapy for 2 years and group A+IT, which received the same maintenance chemotherapy regimen plus, on day 15, injection of viral oncolysate. Of the 107 patients, 57 (53%) achieved complete remission, 29 then being randomized to group A, 28 to group A+IT. As of August 1984, there is no statistical difference between the survival times of the two groups (p = 0.288). Ten years after the start of the study there is still no clear plateau of the survival curve. Nine percent of all patients (18% of the remission patients) are alive today. With the treatment of the mid-seventies, therefore, the cure of a patient suffering from AML was a rare event. The second protocol (SAKK AML 77, from April 1977 to April 1982; 162 patients) was designed to evaluate the usefulness of a prolonged maintenance treatment after early consolidation. The 74 patients who were still in remission after early consolidation treatment were assigned to either maintenance chemotherapy or to observation only. At 3.5 years after the last patient's entry there was no difference between the groups in duration of survival (p = 0.332).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Colony formation in vitro as a prognostic indicator for primary breast cancer.
Cells from some, but not all, tumor biopsy samples form colonies when cultured in semi-solid media. The possibility that colony formation by progenitor cells in these tumors may reflect a more "aggressive" phenotype bearing clinical implications was examined in a series of 61 patients with primary breast cancer. Tumor cells from 32 samples formed colonies in vitro. There was no correlation between colony formation and any of the standard clinical parameters such as tumor size, nodal status, metastatic spread, or hormone receptor levels. Eighteen patients had inflammatory, locally advanced and/or detectable metastatic breast cancer at the time of surgery. Sixteen of these patients have progressed and 15 have died, with no relationship between colony formation and survival. For the 43 remaining patients, 23 had a tissue sample that gave rise to colonies in vitro; 14 of these have relapsed, with a median relapse-free survival (RFS) of 37.6 months, and eight have died with a median survival time of 46.8 months. This is compared with four relapses (median RFS not reached, P = .0043, Peto-Pike), and four deaths (median not reached, P = .1175) in the group without growth of the tumor specimen. These results indicate that colony formation is an independent prognostic parameter for breast cancer, which may be useful for selecting patients who would benefit from more intensive therapy.
Adult↗
[Tumor necrosis factor and cachectin. The same hormone with multiple effects].
Tumor necrosis factor (= TNF) is a polypeptide hormone produced mainly by macrophages and so named according to its cytostatic and cytocidal properties. Its recent structural and functional characterization has led to the recognition of its multiple effects: TNF administration elicits a state of shock with multi-organ lesions, reminiscent of endotoxinemia, and induces wasting similar to the one associated with chronic debilitating diseases, justifying its denomination as cachectin. At a cellular level, TNF exerts a wide range of biological activities, many of them also ascribed to another macrophage-associated cytokine, namely interleukin-1. Its pleotropic effects suggest it might be the mediator of many pathological phenomenons and therefore, attempts at modulating its production might have greater clinical impacts than its use as an antineoplastic agent.
Forecasting↗
Phase II trial of nimustine (ACNU; 3-[4-amino-2-methyl-5-pyrimidinyl) methyl]-1-(2-chloroethyl)-1-nitrosourea hydrochloride) in patients with small cell carcinoma of the lung after failure on combination chemotherapy.
Thirty-nine previously treated patients received Nimustine in a phase II trial to test the therapeutic activity in refractory small cell lung cancer. Nimustine was given as a direct i.v. injection of 100 mg/m2 with treatments repeated every six weeks. Three partial remissions of 56, 123 and 355 days duration were noted among 34 evaluable patients. Thrombocytopenia was prominent with a median platelet nadir of 47,000/microliter. We conclude that Nimustine has minor antitumor-activity in heavily pretreated patients with small cell lung cancer. The definitive value of Nimustine in the treatment of small cell lung cancer, as well as its superiority over its parent compounds remains to be established.
Aged↗
Phase II study of 5'-deoxy-5-fluorouridine (doxifluridine) in advanced malignant melanoma.
Forty-two patients with malignant melanoma were treated with doxifluridine, 4000 mg/m2 daily X 5, repeated every 3 weeks. The daily dose was reduced to 3000 mg/m2 in patients who had experienced severe myelosuppression with prior chemotherapy. A total of 35 patients were evaluable for response, and 25 of these received two or more courses. Two responses were observed. Toxicity mainly took the form of nausea, vomiting, stomatitis, dizziness, ataxia, and fatigue. Mild leukopenia was frequent (43%). Nadir counts less than 1.5 X 10(9)/l leukocytes or 50 X 10(9)/l platelets were seen in 7% and 2% of the courses respectively. Doxifluridine has no useful activity against malignant melanoma.
Drug Evaluation↗