[Palliative home care in Tessin--an example: Lugano Hospice].
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Home Care Services↗
Biomedical subjects
F Cavalli
Publications and source records attributed to F Cavalli.
[Profound venous thrombosis and popliteal cyst: problems of differential diagnosis relative to the use of phleboscintigraphy. Description of a clinical case].
The following is the case report of M. G. a 68-year-old male carrier of polcythemia vera, a pathology in which the risk of thrombosis is increased. The patient presented clinically suspected deep venous thrombosis and a phleboscintigraphy confirmed the diagnosis. A real-time B-mode ultrasonography performed later instead demonstrated a popliteal cyst. The case report focuses on diagnostic methods in deep venous thrombosis and particular attention is paid to the role of phleboscintigraphy, of impedance plethysmography and of real time B-mode ultrasonography.
Aged↗
Dose-finding study of paclitaxel and cyclophosphamide in women with advanced breast cancer.
The primary aim of this study was to define the maximum tolerated doses of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) given by 3-hour infusion and cyclophosphamide given by intravenous bolus every 3 weeks in patients with breast cancer. Patients had received a maximum of one prior chemotherapy for advanced disease. The maximum tolerated dose of the combination was also determined with granulocyte colony-stimulating factor (G-CSF) support. The 80 women who took part in this study received 347 fully evaluable courses of therapy. Starting doses were paclitaxel 135 mg/m2 and cyclophosphamide 750 mg/m2; G-CSF support (5 microg/kg subcutaneously) was added at the subsequent cycle if specific dose-limiting toxicities had occurred during the previous cycle. Febrile neutropenia and severe thrombocytopenia defined the maximum tolerated doses as paclitaxel 200 mg/m2 and cyclophosphamide 2,000 mg/m2, with or without G-CSF support, in patients with or without a prior chemotherapy. Recommended doses were paclitaxel 200 mg/m2 and cyclophosphamide 1,750 mg/m2 in these two groups of patients. The overall response rate was 25% among patients who had received prior therapy for metastatic disease and 50% in patients who had not been previously treated. Complete remissions were reported in 9% of patients, but only among those who were previously untreated.
Antineoplastic Combined Chemotherapy Protocols↗
Lymphoma classification--the gap between biology and clinical management is closing.
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Chromosome Aberrations↗
[Paraplegia following intrathecal chemotherapy].
The occurrence of major neurologic disturbances is a rare complication of intrathecal cytotoxic drug administration. We describe the case of a 30-year old man with relapsed lymphoblastic lymphoma and CNS involvement who was treated by systemic chemotherapy (ESHAP) and intrathecal injections of methotrexate, cytarabine, thiotepa and hydrocortisone. Thereafter he developed persistent paraplegia with sensory and sphincteric insufficiency. The role of the drug in causing this syndrome was suspected when more common causes, such as a meningeal carcinomatosis, had been excluded by means of CNF analysis and radiological examinations. We review this and other published cases and discuss the possible pathogenesis, as well as the clinical and paraclinical findings in paraplegia following intrathecal chemotherapy. Patients particularly at risk are those who receive intrathecal chemotherapy for over CNS disease rather than as prophylaxis, those who receive several injections and patients who are concomitantly treated with radiotherapy to the brain or systemic high-dose methotrexate or cytarabine.
Adult↗
The last 3 months of life of cancer patients: medical aspects and role of home-care services in southern Switzerland.
The clinical data on terminal cancer patients who have died since the establishment of a program of collaboration between community services and the cancer center of Canton of Ticino, southern Switzerland, were retrospectively analyzed to describe the characteristics of patients seen and the effect on them of a home-care program coordinated by the cancer center. The home-care program is based on five geographically grouped community-based domiciliary services, with the addition of one nurse responsible for coordination and one physician from the oncology center. Selection criteria for participation in the home-care program are defined. The main outcome measures were: number of hospitalizations and median hospital stay during the last 3 months of life; reasons for and median length of last hospitalization; place of death of patients who had home care and those who did not. In the group of 993 patients analyzed, the median contact time with the cancer center was 9.5 months (10th percentile: 1 month, 90th percentile: 71 months); the most frequent neoplasm was lung cancer (22%) with the briefest contact time (7.5 months; 10th percentile: 1 month; 90th percentile: 21 months); 13.5% of patients were never hospitalized; half of the patients had a total hospital stay of 24 days or longer and 23% died at home. The sociodemographic and medical characteristics of home-care users were similar to those of the home-care non-users and to those of the overall group. In the group of home-care users (32% of the total) 22% were never hospitalized, half of the patients had a total hospital stay of 17 days or longer, and 43.5% of them died at home. These values were significantly different (P > 0.001) from those reported in the group of home-care non-users. Palliative care, provided at home through community-based domiciliary services, is associated with less frequent and shorter hospitalizations in the last 3 months of life. Medical oncology and palliative treatments should be mutually complementary to improve patients care. Cancer centers should be involved in the planning and coordination of supportive-care domiciliary services.
Aged↗
Clinical and pharmacokinetic study of oral NK611, a new podophyllotoxin derivative.
NK611 is a novel water-soluble podophyllotoxin derivative that has comparable antitumour activity but higher potency and better bioavailability in animals as compared with etoposide. The primary objectives of this study were to determine, after both oral and intravenous administration in the same patient, the bioavailability and the pharmacokinetic profile of NK611. Secondary objectives involved evaluation of the toxicity and the antitumor activity. Patients were randomly assigned to receive oral or intravenous (30-min infusion) doses of 5, 10, and 20 mg/m2 on day 1, when pharmacokinetic studies were performed. A daily oral dose of 20 mg/m2 was then given from day 4 through day 7 for respective total doses of 85, 90, and 100 mg/m2. NK611 and its metabolites were determined in plasma and urine by two different high-performance liquid chromatography (HPLC) methods with UV detection. A total of 21 adult patients entered the study and received the complete first cycle and at least the 1st day of cycle 2; 17 of them received at least 2 complete cycles of treatment. After intravenous administration, the plasma decay curve of NK611 followed a two-exponential model, and after oral administration it declined monoexponentially in most cases. At all dose levels, bioavailability values were around 100%. At concentrations between 10 and 20 mg/m2 after both routes of administration, the pharmacokinetics were nonlinear; the terminal half-life, plasma clearance, and volume of distribution were significantly different; and the area under the plasma concentration-time curve was not correlated to the dose. The urinary excretion of NK611 corresponded to 10-15% of the dose after administration by both routes, whereas that of N-demethyl NK611 and its picroform was highly variable. The features of neutropenia were comparable with those noted for etoposide involving a high degree of interpatient variability and recovery within 1 month after treatment. A daily dose of 20 mg/m2 for 5 consecutive days every 4 weeks is the recommended regimen for phase II studies in patients who have never been treated or have undergone previous chemotherapy only once.
Administration, Oral↗
Gut lymphomas.
Gut lymphoma still remains the subject of much debate and controversy with respect to pathological classification, clinical staging and treatment. This is mainly due to the fact that most studies reported retrospective non-randomized evaluations of small series and lacked uniformity in histological classification, patients' characteristics and type of treatment. Moreover, most of the historical series were published before the recognition of MALT as the origin of most GI lymphomas. Hence, there is a compelling need for the use of modern histological criteria for primary GI lymphomas because of their unique histology, special features and origin in mucosal tissue. General adoption of the histological classification proposed in 1988 by Isaacson et al (Table 1) can be recommended which follows the general principles of the Kiel Classification and includes the MALT lymphomas as a particular disease entity. Combination chemotherapy is the treatment of choice for gut lymphomas with aggressive histology and multiple node involvement or disseminated disease. The effectiveness of combination chemotherapy in advanced disease has excited a reconsideration of the role of primary surgery in less advanced cases where surgery has, historically, been the initial procedure of choice. This is particularly true for gastric lymphomas where it is possible that, in future, surgery will be resorted to as a potential approach for salvage when complete remission is not achieved with conservative therapy. For primary intestinal lymphoma, however, there are as yet no studies which clearly demonstrate that surgery is not necessary. With respect to the group of localized low-grade MALT lymphomas of the stomach and the indolent nature of the disease make plausible a conservative approach, with antibiotic eradication of H. pylori as the sole initial treatment. This may avert or at least postpone the indication for surgical resection in the majority of patients.
Gastrointestinal Neoplasms↗
Initial prognostic factors in small-cell lung cancer patients predicting quality of life during chemotherapy. Swiss Group for Clinical Cancer Research (SAKK).
The question of whether initial prognostic factors in small-cell lung cancer patients have a predictive value for patients' quality of life (QL) during chemotherapy is addressed in the context of a randomised clinical trial comparing early and late alternating chemotherapy (SAKK protocol 15/84). The relative impact of initial tumour stage and performance status, previous weight loss, sex and age on patient-rated QL was analysed over six chemotherapy cycles in 124-130 patients (according to available QL data) with more than 400 questionnaires. Fatigue/malaise, personal functioning, emotional and general well-being were prospectively selected as QL indicators. Predefined summary measures (average QL score over chemotherapy cycles, 'minimum', 'maximum' and 'final' improvement) were analysed separately by scale in various patient groups. General linear models adjusted for treatment arm and response were used to confirm the univariate findings. Within the overall sample, the average QL scores over six cycles were predicted by initial prognostic factors. Patients with poor prognostic factors reported worse QL. Within a limited sample (with baseline QL), patients with poor prognostic factors reported worse QL at baseline and greater improvement under treatment. Graphical comparison of QL patterns over cycles showed permanent discrimination by levels of prognostic factors. The impact of initial prognostic factors was consistently confirmed in the three analyses. Levels of performance status and weight loss best discriminated QL. Initial tumour stage, performance status and previous weight loss can predict QL in small-cell lung cancer during chemotherapy, even after controlling for response to treatment. Our results may contribute to clinical decision-making with regard to the intensity of chemotherapy and QL outcome, especially in patients with extensive disease.
Antineoplastic Combined Chemotherapy Protocols↗
Clinical significance of bcl-2 (MBR)/JH rearrangement in the peripheral blood of patients with diffuse large B-cell lymphomas.
BACKGROUND: Approximately one-fourth of diffuse large B-cell lymphomas (DLCL) carry the bcl-2(MBR)/JH rearrangement caused by the t(14;18) translocation. The clinical significance of this rearrangement in patients with DLCL remains controversial. By polymerase chain reaction (PCR) we prospectively evaluated the prognostic relevance of the bcl-2 (MBR)/JH rearrangement present in circulating B-cells at the time of diagnosis. MATERIALS AND METHODS: The bcl-2 (MBR)/JH rearrangement was analysed by a nested-PCR method in peripheral blood samples of 51 HIV-negative patients with previously untreated DLCL. RESULTS: The bcl-2 (MBR)/JH rearrangement was detected in 16 cases (31%). Peripheral blood bcl-2 (MBR)/JH rearrangement detection by PCR at diagnosis was correlated with poor overall survival, lymphoma-specific survival and time to progression (log-rank P < 0.05). There was no statistically significant difference between the clinical characteristics at presentation of bcl-2/JH-positive and negative patients. CONCLUSIONS: The peripheral blood is a readily accessible tissue for this type of analysis, and this study indicates that detection of the t(14;18) translocation at presentation in the blood of patients with DLCL may presage a poor prognosis.
Chromosomes, Human, Pair 14↗
The effect of adjuvant prednisone combined with CMF on patterns of relapse and occurrence of second malignancies in patients with breast cancer. International (Ludwig) Breast Cancer Study Group.
BACKGROUND: The addition of low-dose prednisone (p) to the adjuvant regimen of cyclophosphamide, methotrexate, 5-fluorouracil (CMF) allowed patients to receive a larger dose of cytotoxics when compared with those on CMF alone. However, disease-free survival and overall survival were similar for the two groups. To test the hypothesis that low-dose prednisone might influence the efficacy of the cytotoxic regimen used, the toxicity profiles of the two treatment regimens and the patterns of treatment failure (relapse, second malignancy, or death) were examined. PATIENTS AND METHODS: 491 premenopausal and perimenopausal patients with one to three positive axillary lymph nodes included in International (Ludwig) Breast Cancer Study Group (IBCSG) trial I from 1978 to 1981 and randomized to receive CMF or CMFp were analyzed for differences in long-term outcome and toxic events. The 250 patients assigned to CMF and prednisone received on the average 12% more cytotoxic drugs than those who received CMF alone. RESULTS: The 13-year DFS for the CMFp group was 49% as compared to 52% for CMF alone, and the respective OS percents were 59% and 65%. Several toxic effects such as leukopenia, alopecia, mucositis and induced amenorrhea were reported at a similar incidence in the two treatment groups. Using cumulative incidence methodology for competing risks, we detected a statistically significant increase in first relapse in the skeleton for the CMFp group at 13 years follow-up with a relative risk (RR) of 2.06 [95% confidence interval (CI), 1.23 to 3.46; P = 0.004]. Patients with larger tumors in the CMFp regimen were especially subject to this increase with a RR for failure in the skeleton of 3.32 (95% CI, 1.57 to 7.02; P = 0.0005). CMFp-treated patients also had a larger proportion of second malignancies (not breast cancer), with RR of 3.34 (95% CI, 0.91 to 12.31; P = 0.09). CONCLUSIONS: Low-dose continuous prednisone added to adjuvant CMF chemotherapy enabled the use of higher doses of cytotoxics. This increased dose had no beneficial effect on treatment outcome, but was associated with an increased risk for bone relapses and a small, not statistically significant increased incidence of second malignancies. The effects of steroids, which are widely used as antiemetics (oral or pulse injection) together with cytotoxics, should be investigated to identify their influence upon treatment outcome.
Antineoplastic Agents, Hormonal↗
First-line fadrozole HCI (CGS 16949A) versus tamoxifen in postmenopausal women with advanced breast cancer. Prospective randomised trial of the Swiss Group for Clinical Cancer Research SAKK 20/88.
BACKGROUND: In a phase III randomized trial, we compared the effectiveness and tolerability of fadrozole (CGS 16949A), a non-steroidal aromatase inhibitor, to tamoxifen as first-line endocrine therapy in postmenopausal women with advanced breast cancer. PATIENTS AND METHODS: Two hundred twelve eligible patients were randomized to receive tamoxifen 20 mg daily, or fadrozole 1 mg twice daily orally until disease progression or the advent of undue toxicity. The treatments were to be discontinued upon disease progression. RESULTS: Prognostic factors were well balanced between the treatment groups, except for sites of metastatic disease. Fadrozole-treated patients had significantly more visceral, especially liver, involvement and less bone-dominant disease. Response rates for fadrozole and tamoxifen were similar, 20% and 27% (95% Confidence Limits (CL): 13%-29% and 21%-35%), respectively. Time to treatment failure was longer in patients randomized to tamoxifen (8.5 months for tamoxifen vs. 6.1 months for fadrozole), but did not reach statistical significance after adjustment for prognostic factors (P = 0.09). Fadrozole, for which a significantly lower percentage of clinically relevant toxic effects (WHO toxicity grade > or = 2) was recorded (27% vs. 13%, respectively; P = 0.009), was better tolerated than tamoxifen. Severe cardiovascular events including 3 fatalities were seen only in patients treated with tamoxifen. Eighty-two patients crossed over to tamoxifen and 66 patients to fadrozole. Crossover endocrine therapy led to response or stable disease in 64% of the patients. The overall survival times of the two treatment groups were similar. CONCLUSIONS: Fadrozole and tamoxifen showed similar efficacy as first-line treatments in postmenopausal patients with advanced breast cancer. Fadrozole was significantly better tolerated and may therefore be an appropriate alternative to tamoxifen, especially for patients predisposed to thromboembolic events.
Adult↗
Low-dose continuous intravenous infusion of 5-fluorouracil for metastatic breast cancer.
BACKGROUND: Third-line chemotherapies for advanced breast cancer are difficult to tailor to the individual patient because of reduced tolerance and significant toxicity. Treatment with a continuous intravenous infusion of low-dose 5-fluorouracil (FU-LDCI) is generally well tolerated and thus, a reasonable option for heavily pretreated patients. PATIENTS AND METHODS: From 1989 to 1995, 106 consecutive patients with advanced breast cancer were treated with FU-LDCI. 5-Fluorouracil was given at an initial daily dose of 250 mg/m2 administered continuously with the aid of an elastomer, non-electronic pump through a permanent central venous line for 21 days followed by a 7-day rest. The median age was 56 years (range, 30-82), the median ECOG Performance Status was 1 (range 0-4) and the median number of metastatic sites was 2 (range 1-4). Sixty-one percent of the patients had previously received more than 2 chemotherapy regimens which in 81% included adriamycin, and in 90% 5-fluorouracil. RESULTS: Eighty patients were evaluable for objective response: 17 of them had partial responses (21%, 95% CI: 14%-31%) and 23 stable disease (29%, 95% CI: 20%-40%). One-hundred five patients were evaluable for subjective response, with 46 reporting improvement (44%, 95% CI: 35%-54%). Previous treatments with either 5-fluorouracil or adriamycin did not predict response to FU-LDCI. Median time to progression for patients with a partial response or stable disease was 259 days (range 82-737). The overall survival for the populations as a whole was 274 days (range 13-2264), and the median dose received was 1904 mg/week (range 753-4329). The main toxic effects were grades I and II mucositis, and nausea and vomiting (observed in 31% and 28%, respectively). Grade III toxicities were uncommon: mucositis in 3%, nausea and vomiting in 3%, anemia, thrombocytopenia and hepatitis in 2%, and skin toxicity (hand-foot syndrome) in 1%. Catheter-related thrombosis was observed in 2% of the patients, and there were no pump failures. A questionnaire concerning the impact of the treatment upon quality of life was completed by all of the 13 patients who were alive at the time of evaluation of the results, and all of them rated FU-LDCI as easy to tolerate. The monthly cost of FU-LDCI (US$1,051.00 in Switzerland) was lower than the cost of weekly low-dose adriamycin (US$1,483.00 in Switzerland), a treatment which is often used as a palliative regimen in similar circumstances. CONCLUSION: FU-LDCI is a useful, cost-effective third-line treatment for patients with metastatic breast cancer who need palliation with cytotoxic drugs.
Adult↗
Phase I clinical and pharmacokinetic study of carzelesin (U-80244) given daily for five consecutive days.
Carzelesin (U-80244), one of the synthetic DNA minor groove binding cyclopropylpyrroloindole analogues, was selected for clinical development because of its high potency, promising antitumor activity in murine solid tumors and leukemia, and significant therapeutic efficacy against colon and rhabdomyosarcoma xenografts. In this Phase I study, carzelesin was given daily for 5 consecutive days to (a) determine the maximum tolerable dose (MTD) and the pattern of toxicity of this schedule; (b) define the pharmacokinetic profile of the parent, as was done for the intermediate compound U-76073 and the DNA-reactive agent U-76074; and (c) document any antitumor activity observed. Carzelesin was given as a 10-min infusion with a constant-rate infusion pump. Treatment was repeated every 4 weeks or when blood counts had recovered to normal values. The starting dose of 12 microgram/m2/day was escalated by 20-30% increments until the MTD (defined as the dose leading to grade 4 hematological or grade 3 nonhematological toxicity in at least two of six patients) was reached. Pharmacokinetic studies were planned on days 1 and 5 of the first cycle in at least two patients per dose level. Plasma levels of carzelesin, U-76073, and U-76074 were determined by high-performance liquid chromatography with UV detection and a detection limit of 0.5 ng/ml. Twenty-five patients were entered in the study, and 56 cycles were evaluable for hematological toxicity. Subsequent dose levels evaluated were 24, 30, 35, and 40 microgram/m2. Both neutropenia and thrombocytopenia were dose limiting and cumulative, with a high interpatient variability. Neutropenia occurred earlier (median time to neutrophil nadir and recovery, 15 and 29 days, respectively) than thrombocytopenia (median time to platelet nadir and recovery, 25 and >/=26 days, respectively); there were delays of treatment because of persisting thrombocytopenia in all patients treated at the MTD. At the MTD, the peak plasma concentrations of carzelesin were achieved at the end of the infusion and were higher than those found cytotoxic in vitro against tumor cell lines. Carzelesin was detectable up to a maximum of 1 h after the infusion. Smaller amounts of U-76073 were detectable for a maximum of 30 min only at the MTD, whereas U-76074 was never found. An 8-month partial remission was reported in one previously untreated patient with hepatocellular carcinoma at 40 microgram/m2. The MTD was fixed at 40 microgram/m2 daily; 35 and 30 microgram/m2 are the daily doses recommended for Phase II studies in good- and poor-risk patients. The daily regimen for 5 days seems to offer no advantage over the single intermittent schedule that has been selected for the Phase II program in Europe.
Adult↗
Phase I study of the antipurine antifolate lometrexol (DDATHF) with folinic acid rescue.
Lometrexol (5,10-dideazatetrahydrofolic acid) is a new antifolate that is highly selective in inhibiting the key enzyme of purine synthesis glycinamide ribonucleotide formyltransferase. The most promising preclinical features of lometrexol in animal models were its significant activity against a broad panel of solid tumors, the schedule dependency of its antitumor activity, and the availability of a rescue regimen with folinic or folic acid. In the present study, lometrexol was first given daily for 3 consecutive days, repeated every 4 weeks (part I). The occurrence of delayed myelotoxicity prompted the development of a rescue regimen with lometrexol given in a single dose on day 1, followed by oral folinic acid, 15 mg four times a day, from day 3 to day 5 (part II). Longer time intervals between administration of lometrexol and start of rescue were then evaluated (part III), and in the last part of the study (part IV), the maximum tolerated dose of single intermittent doses of lometrexol with folinic acid given from day 7 to day 9 was established. Sixty adult patients entered the study. In part I, the highest daily dose that could be safely given was 4 mg/m2, for a total dose of 12 mg/m2. Cumulative early stomatitis and delayed thrombocytopenia were dose limiting. The use of oral folinic acid made it possible to escalate the dose up to 60 mg/m2, and the maximum tolerated dose was reached at this dose when folinic was given from day 7 to day 9, with anemia being the dose-limiting toxicity. A shorter time interval between lometrexol and folinic acid administrations (from day 5 to day 7) is recommended for Phase II evaluations to optimize the antitumor effect. Anemia was normochromic and macrocytic, possibly due to a deficiency of folic acid. One partial response of 8 months' duration was reported in a patient with epithelial cancer of the ovary, relapsing after cisplatin and alkylating agents. The use of folic acid as rescue, proposed on the basis of experimental data and pharmacological considerations, has also allowed the repeated administration of lometrexol at doses higher than in the previous studies. The advantages of rescue with folinic acid over supplementation with folic acid, however, are difficult to define.
Adult↗
[Are all lymphomas or only gastric lymphomas associated with infection?].
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Helicobacter Infections↗
Eradication of Helicobacter pylori infection in primary low-grade gastric lymphoma of mucosa-associated lymphoid tissue.
OBJECTIVE: To determine the effect of eradicating Helicobacter pylori infection on the course of low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma. DESIGN: Prospective cohort study. SETTING: University internal medicine clinics, a referral oncology center in southern Switzerland, and a gastroenterology referral center in northern Italy. PATIENTS: 26 patients with localized primary low-grade gastric MALT lymphoma. INTERVENTION: Treatment for H. pylori infection (bismuth or omeprazole or both, amoxicillin, and metronidazole for 14 days). MAIN OUTCOME MEASURES: Endoscopic biopsy specimens of the gastric mucosa were obtained every 3 to 6 months after treatment for H. pylori infection. RESULTS: Helicobacter pylori was completely eradicated in 25 of 26 patients, but 4 patients needed second-line antibiotic treatment to eradicate the microorganism. Disappearance or almost total regression of the lymphomatous tissue was observed in 15 of the 25 evaluable patients (60%; CI, 39% to 79%); however, disappearance or almost total regression was evident in the first biopsy specimen after treatment for H. pylori infection in only 8 of the 15 patients. CONCLUSIONS: Our study confirms recent anecdotal reports of regression of gastric MALT lymphoma after eradication of H. pylori and indicates that the growth of these extranodal lymphomas may depend on H. pylori.
Adult↗
Recent advances in the management of lymphoma.
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Antineoplastic Combined Chemotherapy Protocols↗