Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 23
Filter
1.
Anticancer Res ; 29(2): 777-83, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19331235

ABSTRACT

The combination of mediastinal radiotherapy (RT) and polychemotherapy (CT) regimens can produce late toxic pulmonary and cardiac effects which often remain at the subclinical level. The aim of the present study was to investigate the cardiopulmonary response to exercise in this kind of patient. Therefore, 126 patients suffering from Hodgkin's disease were investigated after a follow-up of at least 5 years from the completion of the combined treatment. Sixty-two patients had been submitted to ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine)-RT, 40 to ABVD-MOPP (mechloretamine, vincristine, procarbazine, prednisone)-RT and 24 to VEBEP (vincristine, epidoxorubicin, bleomycin, cyclophosphamide, etoposide, prednisone)-RT. The patients were divided into three groups on the basis of respiratory function: group 1 (67 patients), normal spirometry and lung transfer function for carbon monoxide (DLCO); group 2 (52 patients), normal spirometry and DLCO less than 80% of predicted; and group 3 (7 patients), total lung capacity and DLCO less than 80% of predicted. The patients were submitted to respiratory function evaluation and 2D-echocardiography before exercise, and to the determination of cardiac output by the acetylene rebreathing method before and during symptom-limited exercise on a cycloergometer using an incremental protocol. The patients of group 3 and to a lesser extent the patients of group 2 showed, in comparison to patients of group 1, a lower tolerance to exercise, a lower oxygen consumption, a higher respiratory rate, a lower O2 pulse and a lower cardiac output per oxygen uptake. These data indicated an abnormal exercise physiology in the patients with persistent pulmonary impairment, especially when the reduction of DLCO was associated with a decrease of total lung capacity. The lower exercise capacity seems to be due to a combination of decreased cardiac performance and an impairment of gas diffusion capacity.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cardiovascular Diseases/etiology , Exercise/physiology , Hodgkin Disease/physiopathology , Lung Diseases/etiology , Radiation Injuries/physiopathology , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bleomycin/administration & dosage , Bleomycin/adverse effects , Cardiovascular Diseases/chemically induced , Cardiovascular Diseases/physiopathology , Combined Modality Therapy , Cyclophosphamide/administration & dosage , Cyclophosphamide/adverse effects , Dacarbazine/administration & dosage , Dacarbazine/adverse effects , Doxorubicin/administration & dosage , Doxorubicin/adverse effects , Epirubicin/administration & dosage , Epirubicin/adverse effects , Etoposide/administration & dosage , Etoposide/adverse effects , Female , Hodgkin Disease/drug therapy , Hodgkin Disease/radiotherapy , Hodgkin Disease/therapy , Humans , Lung Diseases/chemically induced , Lung Diseases/physiopathology , Male , Mechlorethamine/administration & dosage , Mechlorethamine/adverse effects , Middle Aged , Prednisone/administration & dosage , Prednisone/adverse effects , Procarbazine/administration & dosage , Procarbazine/adverse effects , Radiation Injuries/etiology , Vinblastine/administration & dosage , Vinblastine/adverse effects , Vincristine/administration & dosage , Vincristine/adverse effects , Young Adult
2.
Cancer Invest ; 21(2): 185-92, 2003 Apr.
Article in English | MEDLINE | ID: mdl-12743983

ABSTRACT

Mediastinal irradiation combined with chemotherapy in patients with Hodgkin's disease have been associated with cardiopulmonary toxic effects that can last over the years. In this study we monitored pulmonary and cardiac function in 39 patients affected by advanced Hodgkin's disease (stage II B-III and IV) with mediastinal involvement and submitted to an intensive chemotherapy regimen (epirubicin, vincristine, ciclophosphamide, and etoposide) followed by involved field irradiation. Pulmonary function was verified with chest x-ray, spirometric parameters, arterial blood gas analysis, single breath CO transfer factor (DLCO), and its components Dm and Vc. Cardiac function was verified with electrocardiogram (EKG) and left ventricular ejection fraction (LVEF) by means of radionuclide angiocardiography. The median follow-up was 40 months. Spirometric parameters did no show modifications at the end of treatment, on the contrary they improved during the follow-up. Chest x-ray showed radiographic parenchimal damage in 51% of patients. DLCO remained constantly decreased. sEKG did not show significant modification, whereas LVEF significantly decreased at the end of treatment and remained persistently decreased during follow-up. None of the patients with reduction of DLCO or LVEF showed clinical symptoms of heart and pulmonary dysfunctions. One patient, 49 years old, suffered from myocardial infarction 25 months after the completion of radio-chemotherapy. These data indicate that this combined regimen can induce persistent pulmonary and cardiac damages at subclinical level.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Hodgkin Disease/drug therapy , Hodgkin Disease/radiotherapy , Mediastinal Neoplasms/drug therapy , Mediastinal Neoplasms/radiotherapy , Adolescent , Adult , Antineoplastic Combined Chemotherapy Protocols/toxicity , Combined Modality Therapy/adverse effects , Cyclophosphamide/administration & dosage , Electrocardiography/drug effects , Epirubicin/administration & dosage , Etoposide/administration & dosage , Female , Follow-Up Studies , Heart/drug effects , Heart Function Tests , Humans , Lung/drug effects , Male , Middle Aged , Radiotherapy Dosage , Respiratory Function Tests , Retrospective Studies , Time Factors , Vincristine/administration & dosage
3.
Am J Clin Oncol ; 23(1): 18-21, 2000 Feb.
Article in English | MEDLINE | ID: mdl-10683067

ABSTRACT

Radiotherapy (RT) in patients with favorable-stage Hodgkin's disease can induce clinical and subclinical evidence of pulmonary damage lasting over the years. In this study, we monitored 36 patients with stage IA-IIA Hodgkin's disease treated with subtotal nodal RT. The planned dose of RT was 40 Gy to 44 Gy to the involved areas and 36 Gy to the adjacent uninvolved areas. Pulmonary function was evaluated by chest radiograph, spirometric parameters, arterial blood gas analysis, and single-breath CO transfer factor (DLCO). The tests were performed before and at the end of irradiation, and during the follow-up 1 and 3 to 5 years after the treatment. At the end of RT, we found a significant decrease of total lung capacity, vital capacity, forced expiratory volume in 1 second, residual volume, and DLCO. Spirometric parameters improved during the follow-up period, whereas the decline of DLCO (-6.4%) was persistent. No correlation was found between mantle RT dose and DLCO changes. Four patients showed a decline of DLCO of >20% from pretreatment values but only one was symptomatic. Our study confirms that RT induces a pulmonary-restrictive disease at a subclinical level that seems to be reversible in the majority of patients.


Subject(s)
Hodgkin Disease/radiotherapy , Radiation Pneumonitis , Adolescent , Adult , Aged , Female , Hodgkin Disease/pathology , Humans , Male , Middle Aged , Neoplasm Staging , Radiation Pneumonitis/diagnosis , Radiation Pneumonitis/physiopathology , Radiotherapy Dosage , Remission Induction , Respiratory Function Tests
4.
Skeletal Radiol ; 28(7): 415-21, 1999 Jul.
Article in English | MEDLINE | ID: mdl-10478625

ABSTRACT

We present a case of multifocal osteosarcoma (MFOS) arising 11.5 years after successful treatment of bilateral retinoblastoma. The clinical, imaging and pathological findings at onset, after therapy, and during follow-up are described. Fluorescent in situ hybridization did not reveal a deletion of the RB-1 retinoblastoma gene, although the presence of an inactivating mutation invisible to this method cannot be ruled out. The MFOS may have been a second multifocal tumor associated with the original retinoblastoma or a post-irradiation sarcoma with extensive metastases.


Subject(s)
Bone Neoplasms/diagnosis , Neoplasms, Radiation-Induced/diagnosis , Osteosarcoma/diagnosis , Retinal Neoplasms/diagnostic imaging , Retinoblastoma/radiotherapy , Adolescent , Bone Neoplasms/etiology , Bone and Bones/diagnostic imaging , Female , Humans , Osteosarcoma/etiology , Radiography , Radionuclide Imaging
5.
Radiol Med ; 97(1-2): 42-7, 1999.
Article in Italian | MEDLINE | ID: mdl-10319098

ABSTRACT

INTRODUCTION: A prospective comparative study with pathology was performed at the National Cancer Institute, Milan, to assess the clinical value of Computed Tomography (CT) and endoscopic ultrasound (EUS) for nodal staging in lung cancer. MATERIAL AND METHODS: In three years, 71 patients with histological diagnosis of non-small-cell lung cancer were operated on. They underwent CT and EUS examinations to identify mediastinal lymphadenopathies after major nodal involvement had been excluded by chest X-ray. Diagnostic staging was completed in two weeks prior to treatment. Patients received complete tumor removal and radical lymphadenectomy (55 patients), invasive staging with node resection and sampling (11 patients), or mediastinoscopy (5 patients). Blinded interpretation of CT alone, EUS alone, and CT and EUS together were performed, with systematic correlation of imaging findings and pathological results. RESULTS: The frequency of mediastinal involvement was 42.2%. A total of 329 nodal stations were dissected or sampled and 755 lymph nodes were examined at histology. On a per-station basis, CT had greater sensitivity (74%) than EUS (56%), but EUS was more specific (83.4% vs 92.7%). The accuracy rates of the two techniques were similar (CT 81%, EUS 83%). A site by site analysis showed highest sensitivity (100%) in the lower right paratracheal nodes for CT, and in the superior left paratracheal and subcarinal nodes for EUS. When the EUS and CT images were studied together by specialists on a per-station basis, sensitivity, specificity, and accuracy increased to 85%. CONCLUSIONS: Endoscopic ultrasound should be part of the routine preoperative diagnostic approach to non-small-cell lung cancer, because of its high specificity. Results can be improved when EUS and CT are combined, which suggests that these imaging modalities should be used together in selected patients for the noninvasive staging of non-small-cell lung cancer to identify local lymphatic spread.


Subject(s)
Lung Neoplasms/diagnostic imaging , Lung Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Esophagoscopy , Female , Humans , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Staging , Prospective Studies , Radiography , Sensitivity and Specificity , Ultrasonography
7.
Pediatr Hematol Oncol ; 14(6): 585-8, 1997.
Article in English | MEDLINE | ID: mdl-9383812

ABSTRACT

We present the case of a 19-year-old male who suffered from Langerhans cell histiocytosis (LCH) 12 months after having been treated for recurrent Hodgkin's disease (HD). Immunophenotypic characterization and electron microscopic analysis were useful for the exclusion of a bone relapse of Hodgkin's disease or any other differential diagnosis. The association of LCH with HD or other malignancies is rare but more frequent than previously believed. The significance of such an association and the pathophysiology of LCH are still open questions.


Subject(s)
Histiocytosis, Langerhans-Cell/etiology , Hodgkin Disease/complications , Adult , Humans , Male
8.
Breast Cancer Res Treat ; 44(3): 255-60, 1997 Jul.
Article in English | MEDLINE | ID: mdl-9266105

ABSTRACT

The aim of the present study was to evaluate the clinical activity and side effects of a combination chemotherapy consisting of a five-day continuous infusion of fluorouracil and i.v. vinorelbine in metastatic previously treated breast cancer patients. The patient population was represented by 28 women with evaluable disease, previously subjected to chemotherapy, including anthracycline-containing regimens in 89% of patients. Treatment consisted of five-day infusion of 700 mg/m2/day of fluorouracil and vinorelbine, 20 mg/m2 i.v. bolus on day 1 and 6. In the absence of Grade > 3 leukopenia and stomatitis, cycles were repeated every three weeks, for a total of six cycles. Four complete and thirteen partial responses were documented, accounting for a response rate of 61% (95% CI: 40.5-78.5); the clinical efficacy was high even in patients unresponsive to prior anthracycline treatment. The median response duration calculated from the first drug injection was 8 months (range 4-11). Treatment was well tolerated, with 4% Grade 4 stomatitis and 20% Grade 3 leukopenia as the main toxic reactions. This drug combination is active in metastatic previously treated breast cancer patients, is devoid of severe side effects, and warrants further testing.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Breast Neoplasms/drug therapy , Carcinoma/drug therapy , Adult , Aged , Antimetabolites, Antineoplastic/administration & dosage , Antineoplastic Agents, Phytogenic/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Female , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Humans , Infusions, Intravenous , Injections, Intravenous , Leukopenia/chemically induced , Middle Aged , Prospective Studies , Salvage Therapy , Stomatitis/chemically induced , Vinblastine/administration & dosage , Vinblastine/adverse effects , Vinblastine/analogs & derivatives , Vinorelbine
9.
Anticancer Res ; 17(6D): 4739-42, 1997.
Article in English | MEDLINE | ID: mdl-9494599

ABSTRACT

The combination of mediastinal radiotherapy (RT) with chemotherapy (CT) including bleomycin is associated with an increased risk of pulmonary toxicity. The aim of the present investigation was to evaluate late pulmonary effects of RT plus CT consisting of the ABVD regimen in patients suffering from early stage Hodgkin's disease. For this purpose pulmonary function was serially evaluated before, at the end and at least 1 year after therapy in 32 patients (median age 28 years) with Hodgkin's disease stages IA,B-IIA. Treatment consisted of four cycles of ABVD chemotherapy followed by mediastinal irradiation at the median dose of 36 Gy (range 30.6-43.2). At the end of treatment, resting mean pulmonary function tests showed a significant decline of forced expiratory volume in 1 second (FEV1), forced expiratory flow at 25-75%, (FEF25-75%), total lung capacity (TLC), vital capacity (VC) and carbon monoxide diffusing capacity (DLCO). The decline of TLC, VC and DLCO, indicative of a pulmonary defect of restrictive type, persisted 1 year from the end of therapy. Only seven patients developed symptoms of cough and mild shortness of breath with effort. These data confirm that RT combined with short term ABVD result in pulmonary dysfunction that does not seem to have clinical significance.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , Hodgkin Disease/drug therapy , Hodgkin Disease/radiotherapy , Lung/physiopathology , Pulmonary Ventilation/physiology , Radiotherapy/adverse effects , Adolescent , Adult , Bleomycin/administration & dosage , Carbon Monoxide , Dacarbazine/administration & dosage , Doxorubicin/administration & dosage , Female , Forced Expiratory Flow Rates , Forced Expiratory Volume , Hodgkin Disease/pathology , Humans , Lung/drug effects , Lung/radiation effects , Male , Mediastinum , Middle Aged , Pulmonary Ventilation/drug effects , Pulmonary Ventilation/radiation effects , Radiotherapy/methods , Spleen , Vinblastine/administration & dosage , Vital Capacity
10.
Tumori ; 82(6): 603-9, 1996.
Article in English | MEDLINE | ID: mdl-9061074

ABSTRACT

AIMS: To analyze the radiologic characteristics, clinical course and long-term follow-up of 7 radiologically uncommon pediatric cases of Langerhans cell histiocytosis and to identify prognostic factors related to imaging patterns. METHODS: The clinical records and complete imaging data of 75 patients with LCH diagnosed and treated at the National Cancer Institute of Milan between January 1975 and December 1993 were analyzed, and 43 cases presenting as unifocal bone lesions were identified. The plain film, computed tomography and magnetic resonance characteristics enabled the identification of 7 radiologically aggressive and rapidly progressive cases, which were analyzed at presentation and during follow-up. RESULTS: Although at disease presentation bone lesions appeared lytic destructive, rapidly progressive and often involved adjacent soft tissues, after adequate therapy the disease course was invariably benign and led to almost complete restoration of normal structure and function. Long-term follow-up confirmed the favorable outcome and lack of disease recurrence in all cases. CONCLUSIONS: There is no correlation between radiologically aggressive characteristics and final outcome in Langerhans cell histiocytosis. Radiologists and pediatric oncologists should be acquainted with less common radiologic forms which, at presentation, can mimic more ominous diseases. If recognized and adequately treated, monostotic forms almost invariably have a benign prognosis.


Subject(s)
Histiocytosis, Langerhans-Cell/diagnostic imaging , Adolescent , Child , Child, Preschool , Diagnosis, Differential , Humans , Infant , Magnetic Resonance Imaging , Prognosis , Tomography, X-Ray Computed
11.
J Clin Oncol ; 14(2): 628-35, 1996 Feb.
Article in English | MEDLINE | ID: mdl-8636780

ABSTRACT

PURPOSE: We compared hematologic and clinical effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) after treatment with high-dose cyclophosphamide (HD-CTX, 7 g/m2), given as the first phase of a high-dose sequential chemotherapy program that includes a myeloablative therapy with mobilized progenitor cell autografting. PATIENTS AND METHODS: Forty-nine consecutive patients with non-Hodgkin's lymphoma, Hodgkin's disease, or poor-prognosis breast cancer received GM-CSF (n = 27) or G-CSF (n = 22) after HD-CTX in two consecutive, nonrandomized studies. Cytokines were administered in continuous intravenous (i.v.) infusion for 14 to 15 days at a median dose of 5.5 and 10 micrograms/kg/d, respectively, starting 24 hours after HD-CTX. RESULTS: Neutrophil recovery was faster with G-CSF administration (11.5 v 13.2 days; P = .01), whereas platelet counts recovered more rapidly with GM-CSF (13.7 v 16.6 days; P = .01). Prophylactic platelet transfusions were administered more frequently to patients treated with G-CSF than with GM-CSF (66% v 22% of the patients; P = .02). No clinically significant difference was observed between the two groups concerning days of absolute neutropenia or neutropenic fever. Both cytokines reduced the time to eligibility for subsequent chemotherapy administration compared with historical controls not given cytokine (14 to 16 v 20 days). Both cytokines increased circulation of hematopoietic progenitors. Most side effects were World Health Organization (WHO) median grade 1 to 2, were more frequent during GM-CSF than during G-CSF treatment, and were reversible by simple supportive measures and/or by dose reduction or suspension of the cytokine. Permanent suspension of cytokine administration was never required in either group. CONCLUSION: GM-CSF or G-CSF administration after HD-CTX reduces hematologic toxicity of high-dose chemotherapy and induces circulation of large amounts of hematopoietic progenitors suitable for autografting in cancer patients.


Subject(s)
Antineoplastic Agents, Alkylating/administration & dosage , Breast Neoplasms/drug therapy , Cyclophosphamide/administration & dosage , Granulocyte Colony-Stimulating Factor/therapeutic use , Granulocyte-Macrophage Colony-Stimulating Factor/therapeutic use , Hodgkin Disease/drug therapy , Lymphoma, Non-Hodgkin/drug therapy , Adult , Antineoplastic Agents, Alkylating/adverse effects , Cyclophosphamide/adverse effects , Female , Granulocyte Colony-Stimulating Factor/administration & dosage , Granulocyte-Macrophage Colony-Stimulating Factor/administration & dosage , Humans , Male , Middle Aged
12.
Eur Radiol ; 6(1): 19-24, 1996.
Article in English | MEDLINE | ID: mdl-8797945

ABSTRACT

In this prospective study endoscopic ultrasound (EUS) and computed tomography (CT) were evaluated to compare diagnostic accuracy of the two methods. They were performed for nodal staging in selected patients admitted to our institution for non-small-cell lung cancer (NSCLC). From February 1992 to July 1993, 45 patients were recruited for the study when N3 and N2 nodal involvement were excluded on standard chest X-ray. All the patients completed EUS and CT exams for staging before treatment. The results of sensitivity, specificity and accuracy were obtained in 30 patients who underwent surgical treatment with macroscopically radical resection of T and N, which allowed a complete surgical and histological comparison of CT and EUS findings. On a per-patient basis CT results were: sensitivity 63.6%, specificity 78.9% and accuracy of 73.3%; on a nodal station basis sensitivity, specificity and accuracy were 70.0%, 85.1% and 81.6%, respectively. The EUS evaluation showed, on a per-patient basis, values of sensitivity 45.5%, specificity 57.9% and overall diagnostic accuracy of 53.3%. On a nodal station basis the results were 50.0%, 86.6% and 78.2%, respectively. The results obtained in the 30 patients when both techniques were taken in association regarding sensitivity (90.9%), specificity (73.7%) and accuracy (80.0%) on a per-patient basis suggest that the association of EUS and CT offers the best approach for preoperative staging of NSCLC.


Subject(s)
Carcinoma, Non-Small-Cell Lung/secondary , Endoscopy , Lung Neoplasms/pathology , Lymphatic Metastasis/diagnosis , Mediastinal Neoplasms/secondary , Tomography, X-Ray Computed , Ultrasonography, Interventional , Adenocarcinoma/diagnostic imaging , Adenocarcinoma/secondary , Adenocarcinoma/surgery , Adult , Aged , Aged, 80 and over , Carcinoma, Large Cell/diagnostic imaging , Carcinoma, Large Cell/secondary , Carcinoma, Large Cell/surgery , Carcinoma, Non-Small-Cell Lung/diagnostic imaging , Carcinoma, Non-Small-Cell Lung/surgery , Carcinoma, Squamous Cell/diagnostic imaging , Carcinoma, Squamous Cell/secondary , Carcinoma, Squamous Cell/surgery , Double-Blind Method , Evaluation Studies as Topic , Female , Humans , Lung Neoplasms/surgery , Lymph Node Excision , Lymphatic Metastasis/diagnostic imaging , Male , Mediastinal Neoplasms/diagnostic imaging , Mediastinal Neoplasms/surgery , Middle Aged , Neoplasm Staging , Prospective Studies , Sensitivity and Specificity
13.
J Clin Oncol ; 13(11): 2688-99, 1995 Nov.
Article in English | MEDLINE | ID: mdl-7595726

ABSTRACT

PURPOSE: To define the maximum-tolerated dose (MTD) and better tolerated sequence of paclitaxel by 3-hour infusion plus bolus doxorubicin (DOX) and to evaluate antitumor efficacy. PATIENTS AND METHODS: Thirty-five women with metastatic breast cancer (dominant visceral metastases in 56%, and involvement of > or = three sites in 67%) who never received chemotherapy of any type were studied. Paclitaxel every 3 weeks (125 mg/m2 starting dose) was increased by 25-mg/m2 steps in subsequent cohorts of patients. DOX (60 mg/m2 fixed dose) was administered 15 minutes before the start of or after the end of paclitaxel for a maximum of eight cycles. Subsequently, patients in continuous response could receive single-agent paclitaxel (175 to 200 mg/m2 every 3 weeks). The drug sequence was alternated in consecutive patients and in the first two cycles. RESULTS: Severe neutropenia that lasted greater than 7 days (n = 4), febrile neutropenia (n = 7) and grade III oral mucositis (n = 6) defined the MTD of paclitaxel at 200 mg/m2 in 34 assessable patients. Grade II peripheral neuropathy occurred in 33% of patients. Six women (18%) developed clinically reversible congestive heart failure (CHF) after a median of 480 mg/m2 total DOX. Drug sequence had no effect on toxicities. High efficacy on all metastatic sites in 32 assessable patients accounted for a 41% complete response (CR) rate (95% confidence interval [CI], 24% to 59%) and 94% overall-response rate (95% CI, 79% to 99%). After a median follow-up of 12 months (range 3 to 18), the median response duration is 8 months (range, 2+ to 18+) for complete responders and 11 months (range 1+ to 15+) for partial responders. CONCLUSION: The rate of CR and incidence of CHF may be an expression of therapeutic and toxic enhancement due to the schedule used in this trial. Until clarification of this possibility, this promising combination should be used in investigational trials.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Heart/drug effects , Adult , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Breast Neoplasms/pathology , Chi-Square Distribution , Doxorubicin/administration & dosage , Doxorubicin/adverse effects , Drug Administration Schedule , Female , Heart Failure/chemically induced , Humans , Infusions, Intravenous , Middle Aged , Neoplasm Metastasis , Neutropenia/chemically induced , Paclitaxel/administration & dosage , Paclitaxel/adverse effects , Peripheral Nervous System Diseases/chemically induced , Remission Induction
14.
Br J Cancer ; 72(4): 1007-12, 1995 Oct.
Article in English | MEDLINE | ID: mdl-7547212

ABSTRACT

The androstenedione derivative, exemestane (FCE 24304), is a new orally active irreversible aromatase inhibitor. Fifty-six post-menopausal advanced breast cancer patients entered this study to evaluate the activity of four low exemestane doses in reducing oestrogen levels. The drug's tolerability and clinical efficacy were also assessed. Exemestane was orally administered to four consecutive groups at daily doses of 25, 12.5, 5 and 2.5 mg, and the changes in oestrogen, gonadotrophins, sex-hormone binding globulin and dehydroepiandrosterone sulphate levels were evaluated. Drug selectivity was studied by measuring 17-hydroxycorticosteroid urinary levels. After 7 days of treatment, mean oestrone and oestradiol levels had decreased by respectively 64% and 65% (a decrease which was maintained over time); in the 2.5 mg group, oestrone sulphate levels also decreased by 74%. Gonadotrophin levels were significantly higher, whereas no changes in the other serum hormone levels or any interference with adrenal synthesis were detected. Treatment tolerability was satisfactory: nausea and dyspepsia were reported in 16% of patients. The overall objective response rate was 18%. In conclusion, exemestane is effective in reducing oestrogen levels at all of the tested doses and shows interesting clinical activity.


Subject(s)
Androstadienes/pharmacology , Antineoplastic Agents/pharmacology , Aromatase Inhibitors , Breast Neoplasms/drug therapy , Enzyme Inhibitors/pharmacology , Adult , Aged , Androstadienes/adverse effects , Androstadienes/therapeutic use , Breast Neoplasms/blood , Estradiol/blood , Estriol/blood , Female , Humans , Luteinizing Hormone/blood , Middle Aged , Sex Hormone-Binding Globulin/analysis
15.
J Natl Cancer Inst ; 87(15): 1169-75, 1995 Aug 02.
Article in English | MEDLINE | ID: mdl-7674322

ABSTRACT

BACKGROUND: To date, anthracyclines are the most active drugs against breast tumors, and the taxane paclitaxel (Taxol) looks very promising. Both classes of drugs are affected by cellular multidrug-resistance mechanisms, and therefore their sequential use raises the possibility of clinical cross-resistance. It is therefore important to assess the activity of paclitaxel in patients with clinical resistance to anthracyclines. PURPOSE: We assessed the safety and efficacy of paclitaxel administered by the logistically convenient 3-hour infusion to breast cancer patients who had disease progression within 12 months since prior therapy with anthracyclines. METHODS: Fifty-one patients with metastatic breast cancer who had all relapsed or whose disease had progressed within 12 months from completion of an anthracycline-containing chemotherapy protocol (six receiving adjuvant therapy, 19 receiving neoadjuvant therapy, and 26 receiving treatment for metastatic disease) were enrolled in this phase II trial from June 1992 to May 1994. After medication to prevent type I acute hypersensitivity reactions, paclitaxel was given intravenously over 3 hours at 175 mg/m2 to the first 15 patients and at 225 mg/m2 to the next 36 patients. The median age was 50 years (range, 31-62 years), and the median Eastern Cooperative Oncology Group performance status was 0 (range, 0-2). RESULTS: Patients received a median of five cycles (range, one to 11 cycles). After initial doses of 175 and 225 mg/m2, paclitaxel could be increased by 25 mg/m2 in 73% and 58% of cycles, respectively. Among 50 assessable patients, seven achieved a complete response and 12 achieved a partial response (response rate, 38% [95% confidence interval = 25%-53%]). The median duration of response was 7 months (range, 4-16 months), and the median time to disease progression for all patients was 5 months. Grade 4 neutropenia occurred in 3% of the cycles and in 12% of the patients and was never associated with fever and infection. Common toxic effects were myalgia and arthralgia (94% of the patients; 4% grade 3), peripheral neuropathy (92% of the patients; 8% grade 3), and alopecia (all patients). Pruritus and neuropathy were significantly more frequent and severe, respectively, with the higher dose (P < .01 by chi 2 test). Frequency and severity of other toxic effects were similar at either starting dose. Ten patients had symptoms of neuro-optic toxicity. Only one patient had a grade 2 hypersensitivity reaction. CONCLUSIONS: Paclitaxel at starting doses of 175 and 225 mg/m2 given as a 3-hour infusion can safely be administered to, and is active in women whose disease has progressed after prior treatment with anthracyclines. There was evidence of increased toxicity at the higher dose but no suggestion of better efficacy. IMPLICATION: Paclitaxel by a 3-hour infusion in combination with doxorubicin should be investigated in patients with metastatic breast cancer. Unless randomized trials demonstrate greater efficacy of the more toxic higher dose, it is suggested that a dose of 175-200 mg/m2 be administered with the 3-hour infusion schedule.


Subject(s)
Antineoplastic Agents, Phytogenic/administration & dosage , Breast Neoplasms/drug therapy , Paclitaxel/administration & dosage , Adult , Antibiotics, Antineoplastic/therapeutic use , Antineoplastic Agents, Phytogenic/adverse effects , Breast Neoplasms/pathology , Disease Progression , Drug Administration Schedule , Female , Humans , Infusions, Intravenous , Middle Aged , Paclitaxel/adverse effects
16.
J Cancer Res Clin Oncol ; 121(6): 378-82, 1995.
Article in English | MEDLINE | ID: mdl-7797604

ABSTRACT

Formestane, a new selective aromatase inhibitor devoid of severe side-effects, has been shown to be active in patients with advanced breast cancer. To investigate the clinical activity and endocrinological effects of formestane as a first-line treatment, 52 patients were administered two different doses: 24 received 250 mg formestane and 28 received 500 mg formestane i.m. fortnightly. All of the patients had a performance status of 2 or less (ECOG scale), 34 (65%) had a disease-free interval of at least 2 years and 21 (40%) were both oestrogen-receptor- and progesterone-receptor-positive; 20 patients received hormone and 13, received chemotherapeutical adjuvant treatment. Objective responses were obtained in 8 patients in the 250-mg group (33%; 95% CI: 14%-52%) and in 13 patients in the 500-mg group (46%; 95% CI: 28%-64%). The median response duration in the two groups was respectively 11 and 12 months. E2 serum levels of oestradiol had significantly (P < 0.001) decreased to more than 40% below the baseline value in both groups after 15 days of treatment, and remained unchanged thereafter. Local and systemic tolerability was satisfactory. We conclude that formestane is an effective and well-tolerated agent in previously untreated patients, and that these results should be confirmed by further studies.


Subject(s)
Androstenedione/analogs & derivatives , Antineoplastic Agents/therapeutic use , Aromatase Inhibitors , Breast Neoplasms/drug therapy , 17-Hydroxycorticosteroids/urine , Aged , Androstenedione/administration & dosage , Androstenedione/therapeutic use , Antineoplastic Agents/administration & dosage , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Drug Administration Schedule , Estradiol/blood , Female , Humans , Injections, Intramuscular , Middle Aged , Postmenopause , Prognosis , Risk Factors , Survival Analysis , Treatment Outcome
17.
Oncol Rep ; 2(1): 63-8, 1995 Jan.
Article in English | MEDLINE | ID: mdl-21597690

ABSTRACT

Megestrol acetate (MA) is one of the most widely used progestins in the palliation of advanced breast cancer, but its optimal dose level has yet to be defined. Forty-six women with progressive advanced disease were given MA according to a monthly loading-dose-schedule (320 mg/day orally) followed by standard-dose maintenance (160 mg/day). Most of the patients had been heavily pretreated with endocrine and/or chemotherapy; all the cases were evaluable. The response rate was 20% (95% CI: 9-31%), with 9 subjects achieving PR. The median time to response was 3 months (range 2-11), the median response duration being 3 months (range 3+-12+). After a median follow-up period of 8 months (range 7-16), only 3 of the patients achieving PR are still on treatment. No increased toxicity or potentially detrimental endocrine effects were observed and all of the patients showed good compliance to treatment. Although the loading-dose schedule used in the present series proved to be feasible, it does not appear to provide any clinical advantage over standard-dose MA treatment.

18.
Tumori ; 80(6): 433-7, 1994 Dec 31.
Article in English | MEDLINE | ID: mdl-7900232

ABSTRACT

AIMS AND BACKGROUND: The number of elderly people is increasing, and the proportion of breast cancer in female cancer patients older than 65 years is 26%. In elderly patients, hormone therapy is widely accepted as the treatment of choice, because of its efficacy and good tolerability compared to chemotherapy. The aim of this study was to evaluate the endocrinologic and clinical activity of formestane (4-hydroxyandrostenedione), a selective aromatase inhibitor, in elderly patients with advanced breast cancer. METHODS: Thirty-five patients older than 65 years, selected from a larger group, were given formestane (250 mg or 500 mg i.m. fortnightly). Patients were evaluable for tumor response after 4 doses of formestane. Blood samples were collected to evaluate E2, FSH, LH, SHBG and DHEAS serum levels at baseline and after 2, 4, 8, 12 and 24 weeks. RESULTS: Thirty patients had PS < or = 1 (ECOG) and only 5 patients had PS = 2. Twenty-six patients were ER positive. Previous hormonal treatment for metastatic disease had been given to 17 patients; only 1 case had received chemotherapy. The overall response rate was 51% (95% C.I. 35-67%) and the median response duration was 9.5 months. Three complete responses were observed on viscera. The best responses were obtained on soft tissues (59%); on bone and viscera the response was respectively 45% and 47%. Local and systemic tolerability was highly satisfactory. Formestane induced prolonged suppression of E2 levels in all of the patients, and a significant reduction in SHBG levels was also observed from month 2 onward. A statistically significant (P = 0.0001) rise in serum FSH was also observed during the therapy. CONCLUSIONS: The study showed that formestane induced a long-lasting suppression of E2 levels and a satisfactory overall response. In our opinion, the drug is an effective and well-tolerated approach in the management of advanced breast cancer in elderly patients.


Subject(s)
Androstenedione/analogs & derivatives , Antineoplastic Agents/therapeutic use , Aromatase Inhibitors , Breast Neoplasms/drug therapy , Aged , Androstenedione/therapeutic use , Breast Neoplasms/pathology , Female , Humans , Prognosis , Risk Factors , Treatment Outcome
19.
Radiol Med ; 87(6): 741-6, 1994 Jun.
Article in Italian | MEDLINE | ID: mdl-8041925

ABSTRACT

The records of 3,795 cases of malignant melanoma treated at the INT (Milan) from 1975 to 1992 were reviewed. Histologic confirmation was obtained in all cases. Thirty-one patients (0.82%) with solitary or multiple skeletal metastases were identified. The review of conventional films, tomograms, CT, MR and bone scintigraphy images enabled us to detect 120 single bone lesions. The X-ray features were divided into two groups according to typical and atypical skeletal lesions. Typical bone metastases are osteolytic (87.5%), with medullary origin (91.6%), and they cannot be distinguished from other osteolytic metastases on the basis of imaging criteria alone. Lesion growth causes cortical erosion and destruction (46.6%), pathologic fractures (22.5%) and soft tissue involvement (12.5%). Lytic areas usually have ill-defined margins. Clear-cut outline is an uncommon finding. Atypical skeletal metastases exhibit a mixed osteolytic-osteoblastic pattern (10%), which is hardly ever completely osteoblastic (2.5%). Other unusual metastatic patterns include intense trabecular rarefaction with no detectable single lesion (3.3%), the presence of a well-defined sclerotic rim and periosteal reaction (12.5%). Atypical growth may cause extensive cortical destruction and periosteal production resembling osteogenic osteosarcoma. The various imaging methods show that conventional radiology has relatively poor sensitivity because of anatomical reasons, while MRI is the most sensitive method to detect skeletal localizations. Treatment changes the radiologic patterns of the lesions: recalcification, sclerotic rim, periosteal reaction are common response patterns. Finally, in spite of the above limitations, conventional radiology remains the method of choice to assess lesion evolution during the follow-up.


Subject(s)
Bone Neoplasms/diagnosis , Bone Neoplasms/secondary , Melanoma/diagnosis , Melanoma/secondary , Bone Neoplasms/epidemiology , Bone and Bones/diagnostic imaging , Bone and Bones/pathology , Follow-Up Studies , Fractures, Spontaneous/diagnosis , Fractures, Spontaneous/epidemiology , Fractures, Spontaneous/etiology , Humans , Italy/epidemiology , Magnetic Resonance Imaging , Melanoma/epidemiology , Osteolysis/diagnosis , Osteolysis/epidemiology , Osteolysis/etiology , Sensitivity and Specificity , Tomography, X-Ray Computed
20.
Tumori ; 79(3): 170-82, 1993 Jun 30.
Article in English | MEDLINE | ID: mdl-8236499

ABSTRACT

AIMS: To highlight the different changes induced in lung tissues by various forms of radiotherapy (RT) according to tumor site and type. METHODS: A retrospective analysis of the roentgenographic evaluation of and long-term follow-up data on 2375 patients who received RT for various intrathoracic and extrathoracic tumors at the National Cancer Institute of Milan. RESULTS: The iconographic patterns of post-RT changes, grouped by site and type of tumor and RT procedure and described in detail, afford deeper insight into a little-known area of lung pathology. CONCLUSIONS: These descriptions of common and uncommon patterns of the irradiated lung as they appear on conventional chest roentgenograms enable the radiologist and radiotherapist to assess exactly the response of tumor and lung tissues and to plan the most appropriate clinical follow-up.


Subject(s)
Lung/radiation effects , Thoracic Neoplasms/radiotherapy , Follow-Up Studies , Humans , Lung/diagnostic imaging , Lung/pathology , Radiography , Retrospective Studies , Thoracic Neoplasms/diagnostic imaging , Thoracic Neoplasms/pathology
SELECTION OF CITATIONS
SEARCH DETAIL
...