[Cell resistance in oncology. Therapeutic prospects].
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Antineoplastic Agents↗
Biomedical subjects
R Rosso
Publications and source records attributed to R Rosso.
Prognostic factors in node positive primary breast cancer patients treated with adjuvant CMF.
The influence of various patient and disease-related parameters on survival (S) and disease-free survival (DFS) in 217 node positive primary breast cancer patients treated with surgery followed by adjuvant i.v. cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) was evaluated by univariate and multivariate analyses. Five year actuarial S and DFS were 73.3% and 54.8%, respectively. Univariate analysis revealed that patient age, number of involved axillary nodes and ER status had a significant impact on both S and DFS. PgR positive tumors had improved DFS but no S difference was observed. Menopausal status predicted S but not DFS. Primary tumor size and CMF-induced amenorrhea did not predict disease outcome. Multivariate analysis demonstrated that only degree of nodal involvement and PgR status had independent significant impact on prognosis. Both S and DFS are significantly influenced by the number of involved nodes, whereas improved DFS but not S was evident in patients with PgR positive tumors.
Adult↗
Phase II study of weekly oxaliplatin and high-dose infusional 5-fluorouracil plus leucovorin in pretreated patients with metastatic colorectal cancer.
BACKGROUND: Chemotherapy with oxaliplatin, fluorouracil (5-FU) and leucovorin (LV) has proven efficacy in patients with advanced colorectal carcinoma (CRC), although the optimal dosage and administration schedule are still unclear. This phase II trial investigated the tolerability and activity of weekly oxaliplatin, high-dose infusional 5-FU and LV in pretreated patients with metastatic CRC. MATERIALS AND METHODS: Patients received weekly courses of i.v. oxaliplatin 50 mg/m2 (1-h infusion), LV 100 mg/m2 (1-h infusion) and 5-FU 2100 mg/m2 (24-h infusion) until disease progression or unacceptable toxicity. NCI-CTC criteria were used for assessment of side-effects (at each cycle) and WHO criteria for assessment of tumour response (every 8 cycles). For descriptive purposes, time to progression, overall survival and duration of objective response were also calculated. RESULTS: Forty-four patients were enrolled and received a total of 606 cycles (median 13/patient, range 4-33), and 70% of courses (421/606) were delivered at 100% of the planned dose. The most frequent side-effects were gastrointestinal and neurological and incidence rates were: diarrhoea 66% (grade III: 29%), nausea/vomiting 54%, neurotoxicity 34% (grade III: 2%), fatigue 27%, mucositis 22%, leucopenia 14%. No grade IV toxicity was observed. Objective response rates were: partial response 23% (10 patients), stable disease 59% (26) and progressive disease 11% (5). Median time to progression was 7 months, overall survival 13 months and the duration of partial response and stable disease were 9 and 6 months, respectively. CONCLUSION: The study demonstrated that this regimen has a favourable tolerability profile and is an active combination in the pretreated metastatic CRC patient, deserving further evaluation in phase III trials.
Aged↗
Alternating chemotherapy with cyclophosphamide, doxorubicin, vincristine and cisplatin, etoposide followed by prophylactic cranial and thoracic irradiation for small cell lung cancer (SCLC): long-term results.
Both CAV (Cyclophosphamide, Doxorubicin, Vincristine) and PE (Cisplatin, Etoposide) are effective and non cross-resistant regimens in the treatment of SCLC. We designed a chemotherapeutic scheme including CAV and PE given in an alternating fashion with the following schedule: Cyclophosphamide 1000 mg/sm, Doxorubicin 50 mg/sm, Vincristine 2 mg/sm I.V. on day 1, alternated every 21 days with Cisplatin 20 mg/sm and Etoposide 80 mg/sm I.V. days 1-5 for 6 cycles. Following chemotherapy (CT) chest radiotherapy in patients (pts) with limited disease (LD) in complete response (CR) or partial response (PR) and prophylactic cranial irradiation (PCI) in CRs were given, 32 pts entered the study and 27 were evaluable: 9/27 (33.3%) had CR (8/15 with LD had CR) and 15/27 (55.5%) PR. The overall median survival was 53.71 weeks: 79.85 weeks for LD pts and 32.86 for ED.4 pts with LD were alive after 2 years and 2 of them are still alive without disease at 44 and 46 months. Toxicity was acceptable in all patients. Alternating chemotherapy with CAV and PE followed by chest and brain RT in responding LD pts is an effective induction treatment for SCLC although long-term survival still remains disappointing.
Antineoplastic Combined Chemotherapy Protocols↗
Hodgkin's disease: update of findings.
The authors critically review the problem of Hodgkin's disease (HD) in the light of new morphological, immunohistochemical, kinetic, genotypic, and virological findings. These support the lymphoid origin of neoplastic Hodgkin's and Reed-Sternberg cells, because of regular expression of the CD30 lymphoid activation antigen and frequent detection of B- or T-cell phenotypic and/or genotypic markers. It is possible to hypothesize the release of cytokines by tumoral elements as well as the presence of specific cytokine receptors on their surface. This might explain some clinical and pathological features, such as fever, loss of weight, eosinophilia and attraction of reactive elements that make up the composite cellular milieu of typical HD. Integration of monoclonal EBV in the genoma of neoplastic elements has repeatedly been shown, and this might play an essential role in the pathogenesis of the disease. On the basis of present concepts, the borderlines between HD and some categories of non-Hodgkin's lymphomas--especially the anaplastic large cell forms--have become somewhat blurred. Additional research work in the field of HD is desirable and might pave the way for new and more effective therapeutic approaches, designed on the basis of the natural history of the neoplasm.
Antigens, CD↗
Radiation treatment plus CCNU plus the radiosensitizer lonidamine in malignant gliomas operated.
From June 1988 to January 1990, 28 patients with primary brain tumours were operated and treated with radiotherapy (RT) (50 Gy whole brain + 10 Gy boost to tumour bed) + cyclohexylnitrosourea (CCNU) 130 mg/msq p.o. every 6 weeks + the radiosensitizer Lonidamine (LND) (150 mg T.I.D. for the whole duration of treatment). Myelotoxicity of this regimen was acceptable, with two cases of grade IV leukopenia and thrombocytopenia requiring discontinuation of treatment. LND was discontinued in 6 patients for major toxicity (myalgias and/or testicular pain), and 3 additional patients required dose reduction of this drug. The median follow-up time of the patients on study was 12 months. The median survival time (MST) was 5 months for grade IV astrocytomas (n = 8) and 16 months for grade III lesions (= 20). No correlation was seen between survival of patients and DNA content, measured by flow cytometry, or levels of O6- alkylguanine-DNA alkyltransferase, an enzyme that repairs the CCNU-induced DNA damage.
Brain Neoplasms↗
Predictive value of some clinical and pathological parameters on upper level axillary lymph node involvement in breast cancer.
The role of radical axillary dissection in breast cancer management is presently under discussion. In this study we have evaluated the relationship between the pattern of metastatic axillary lymph node involvement by level and some of the main prognostic factors (age of the patient, size, grading, estrogen receptor and progesterone receptor status of the primary tumor) in 185 patients with operable breast cancer. The III level appeared to be involved in 31 (16.8%) out the 108 patients with axillary lymph nodes positive for metastases. A discontinuous pattern of axillary involvement (skip metastases) was observed in about 10% of cases. Logistic regression analysis of the data shows that only G3 is significantly correlated with the risk of III level invasion (p less than 0.05). We conclude that, at present, a selection of possible candidates for a less than radical axillary dissection is not as yet feasible. Since the risk for III level invasion cannot be sufficiently defined.
Breast Neoplasms↗
Intraperitoneal chemotherapy with carboplatin and interferon alpha in the treatment of relapsed ovarian cancer: a pilot study.
In ovarian cancer patients intraperitoneal chemotherapy confers pharmacokinetic advantages and appears an attractive way to improve the efficacy of certain antineoplastic agents. Intraperitoneal carboplatin and interferon alpha have been separately evaluated in ovarian cancer "with promising results". We report a phase I-II pilot trial of intraperitoneal carboplatin 400 mg/sqm plus interferon alpha 25 x 10(6) U q 28 d in 16 patients (pts) previously treated with intravenous cisplatin based chemotherapy. All the patients had relapsed (11 pts) or refractory (5 pts) disease; residual tumors were less than 2 cm in 10 pts and greater than 2 cm in 6 pts. Local and general toxicities were moderate, with neither WHO grade 4, nor neurotoxicity and ototoxicity. Myelotoxicity was the most frequent side effect. Among 14 evaluable pts, objective responses were observed in 6 pts (42.8%) including 3 pts with pathologically confirmed complete response (21.4%); six more pts presented prolonged disease-free survival. Response occurred in both categories of pts with greater than or less than 2 cm residual disease, also in pts refractory to prior intravenous cisplatin. The proper role of intraperitoneal treatment cannot be exactly defined without large randomized trials designed to compare intraperitoneal to intravenous drug administrations.
Antineoplastic Combined Chemotherapy Protocols↗
Concomitant radiation-doxorubicin administration in locally advanced and/or metastatic soft tissue sarcomas: preliminary results.
Doxorubicin was administered by continuous infusion at a dosage of 12 mg/sqm/day for 5 days concomitantly with radiation treatment (150 or 200 cGy/day for trunk or extremity lesions, respectively) for 5 days. The 5-day cycles were repeated every 3 weeks. Seventeen patients, 5 of whom were pretreated, entered the study; all were assessable for toxicity and 15 for response. The overall objective response rate was 46% (7/15): 1 complete and 6 partial responses. Response rate reached 54% in only non-pretreated patients (6/11) and 75% in patients with PS less than or = 2 (6/8). No disease progression was observed during treatment. The median duration of complete or partial responses was 28 weeks (range 5-86). Toxicity was low and treatment very well tolerated. In our preliminary analysis, the response rate obtained with this combined chemo-radiotherapic regimen was encouraging and the toxicity was acceptable.
Adult↗
[Medical treatment of breast carcinoma].
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Adjuvants, Immunologic↗
Oral ondansetron (GR38032F) for the control of acute and delayed cyclophosphamide-induced emesis.
The efficacy of the serotonin antagonist ondansetron (GR38032F, Glaxo) was evaluated in the prevention of nausea and vomiting induced by combinations containing cyclophosphamide (CTX) greater than or equal to 600 mg/m2 IV day. At their first treatment course, 55 patients (10 males, 45 females) median age 55 years (range 31-76) were given ondansetron 8 mg orally tds for a minimum of 3 to a maximum of 5 days. 54 patients were evaluable. Complete and major control of acute (day 1) emesis was observed in 94.5% of patients and acute nausea was graded as absent or mild in 83.3% of cases. Complete and major control of emesis improved on subsequent study days from 96.1% on study day 2 to 100% on study day 5. Side effects were mild. Ondansetron is a safe and effective antiemetic drug.
Antiemetics↗
Chemotherapy with mitomycin-C, epidoxorubicin and vinblastine in CMF failing breast cancer patients.
Since most patients with breast cancer are treated with CMF as first line chemotherapy (usually in the adjuvant setting), schedules with alternative drugs are needed for the metastatic disease. In this study a new combination of Mitomycin, Epidoxorubicin and Vinblastine was employed in a group of 24 patients with metastatic breast cancer. A response rate of 37.5% was observed with a mild to moderate toxicity.
Antineoplastic Combined Chemotherapy Protocols↗
Comparison of in vitro drug sensitivity by inhibition of tritium release from [5-3H]-2'-deoxyuridine and a clonogenic assay.
In a search for a rapid and simple method to determine drug-induced cell lethality, the inhibition of tritium release from [5-3H]-2'-deoxyuridine (ITR) was compared with a standard clonogenic assay. Seven drugs were studied. After a 4 hr incubation period, [5-3H]-2'-deoxyuridine was added to cultures of human colon carcinoma cells (HCT-8) in vitro and four dose-response curves were generated for each drug by sampling the culture medium for tritiated H2O formation 4, 24, 48 and 72 hr later. These curves were compared to those obtained by a standard clonogenic assay. The ED50 values for 5 of the 7 drugs tested, methotrexate, 5-fluorouracil, doxorubicin, vincristine and cisplatin, as measured by inhibition of HCT-8 colony growth, were within 3 times the values observed with the metabolic assay. The ITR highly overestimated the cytotoxicity of 5-fluoro-2'-deoxyuridine: the irreversible inhibition of thymidylate synthase by this nucleoside resulted in an ED50 value 100-fold lower than that observed with the clonogenic assay. Opposite results were obtained with 5-fluorouridine. These data indicate that the ITR can be used to determine drug sensitivity of these cells to a host of compounds although it cannot be used indiscriminately for every antineoplastic agent as a cytotoxicity assay.
Adenocarcinoma↗
Reactive hemophagocytosis in Ki-l positive large cell lymphoma: a case study.
A case of large cell lymphoma presenting with hemophagocytic syndrome is reported. The clinicopathological findings suggested a diagnosis of malignant histiocytosis, but on the basis of immunohistological studies Ki-l lymphoma was diagnosed. Neoplastic cells expressed activation antigens such as HLA-DR, IL 2R, T10 and Ki-l, and showed high proliferative activity, but were devoid of T and B cell markers. The high percentage of reactive macrophages found in the bone marrow and lymph node probably reflected the release of lymphokines by the tumor population. The patient was treated with aggressive chemotherapy and is in complete remission at 8 months from diagnosis.
Adolescent↗
Oral chemotherapy for poor risk small-cell lung cancer patients with combined idarubicin and etoposide.
Sixteen patients with previously untreated small-cell lung cancer, unsuitable for standard aggressive intravenous chemotherapy due to advanced age or poor performance status or very advanced disease including brain metastases or either extensive liver or marrow involvement with impaired organ function, were treated with combined oral chemotherapy including 4-demethoxydaunorubicin (IMI30, idarubicin) 30 mg/sm on day 1 and etoposide (VP16) 150 mg/sm on days 2,3,4 every 4 weeks. Out of 13 evaluable patients 1 had a complete response and 2 had a partial response with an overall objective response rate of 23% (95% confidence-limits 5-53.8%). Toxicity was generally very mild. Although the compliance of this regimen is excellent, its antitumor activity seems unsatisfactory even in this category of poor-risk small-cell lung cancer patients.
Administration, Oral↗
Continuous venous infusion of vindesine in metastatic breast cancer: experience with a subcutaneously implanted system and portable pump.
Fourteen patients with advanced pretreated breast cancer were treated with vindesine in continuous venous infusion (1.5 mg/sm/24 hours for 72 hours every 3 weeks). A totally implanted venous access and a portable pump were used. A total of 33 courses was administered. No objective response was observed and treatment was stopped. Drug-related toxicity consisted mainly of alopecia (64% of patients), nausea and vomiting (29%) and mucositis (29%). Catheter - related toxicity was observed in 6 patients (43%) and consisted of infection of the skin pocket in 4 patients and dislodging of the needle and catheter break in one patient. The feasibility of continuous venous infusion of vesicant drugs in outpatients is discussed.
Adult↗
Effect of 17-beta-estradiol on doxorubicin cytotoxicity in human breast cancer cell culture.
Pre-treatment with 17-beta-estradiol appeared to improve the cytotoxic efficacy of doxorubicin on MCF-7 but not on ZR-75-1 and EVSA-T human breast cancer cell lines. MCF-7 and ZR-75-1 are both estrogen receptor-positive cell lines: however, only ZR-75-1 showed improved proliferation in the presence of estradiol. On the other hand MCF-7 appeared basically more resistant to doxorubicin compared to the other cell lines. The results indicate that estrogenic pre-treatment is a potential tool for partially overcoming human breast cell resistance to doxorubicin; moreover, they suggest that the mechanism of interaction could be not exclusively related to actual cytokinetics modulation.
Breast Neoplasms↗
Adjuvant systemic treatment of resectable breast cancer: eleven years results of a monoinstitutional chemo-hormone-immunotherapy trial.
131 patients with resectable, node-positive breast cancer were treated at the National Institute for Cancer Research of Genoa, Italy with a systemic adjuvant regimen based on 14 cycles of chemotherapy, immunostimulation with levamisole, and--for postmenopausal patients--hormone therapy with tamoxifen. The present evaluation is performed eleven years after the admission of the first patient: so far, 75 patients (57.3%) have relapsed and 52 (39.7%) have died. An analysis of prognostic factors for relapse and death shows that the number of positive axillary lymph nodes and the dimension of the primary tumor are significantly associated with survival and relapse-free survival, while age and menopausal status are not.
Age Factors↗