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A Goldhirsch

Publications and source records attributed to A Goldhirsch.

At least 127 records · Page 7Linked to original sources
PubMed1998

Totally implantable central venous access ports for long-term chemotherapy. A prospective study analyzing complications and costs of 333 devices with a minimum follow-up of 180 days.

BACKGROUND: A few data are available from analyses of the complications and costs of central venous access ports for chemotherapy. This prospective study deals with the complications and global costs of central venous ports connected to a Groshong catheter for deliverance of long-term chemotherapy. PATIENTS AND METHODS: Patients with a variety of solid neoplastic diseases requiring chemotherapy who were undergoing placement of implantable ports over a 30-month period (1 October 1994 to 31 March 1997) have been prospectively studied. Follow-up continued until the device was removed or the study was closed (30 September 1997); patients with uneventful implant experience and subsequent follow-ups of less than 180 days were not considered for this study. A single port, constructed of titanium and silicone rubber (Dome Port, Bard Inc., Salt Lake City, USA), was used, connected to an 8 F silastic Groshong catheter tubing (Bard Inc., Salt Lake City, USA). Two-hundred ninety-six devices were placed in the operating room under fluoroscopic control even in the patients treated and monitored in a day-hospital setting: 37 of them were in an angiographic suite. A central venous access form was filled in by the operator after the procedure and all ports were followed prospectively for device-related and overall complications. The average purchase cost of the device was obtained from the hospital charges, based on the costs applied during the 30-month period of the study. Insertion and maintenance costs were estimated by obtaining the charges for an average TIAP implant and its subsequent use; the costs of complication management were assessed analytically. The total cost of each device was defined as the purchase cost plus the insertion cost plus the maintenance cost plus the cost of treatment of the complications, if any. The cost of removing the TIAP was also included in the economic analysis when required by the treatment of the complication. RESULTS: Three hundred thirty-three devices, for a total of 79,178 days in situ, were placed in 328 patients. Five patients received second devices after removal of the first. In all cases the follow-up was appropriate (median 237 days, range 180-732). Early complications included 10 pneumothoraxes (3.4%; six tube-thoracostomies were applied, 1.8%) and six revisions for port and/or catheter malfunction (overall early complications = 16, 4.48%). Late complications comprised five instances of catheter rupture and embolization (1.5%, 0.063 episodes/1000 days of use), five of venous thrombosis (1.5%, 0.063 episodes/1000 days of use), one of pocket infection (0.3%, 0.012 episodes/1000 days of use), and eight of port-related bacteremia (2.4%, 0.101 episodes/1000 days of use). The infections were caused by coagulase-negative Staphylococcus aureus (five cases), Bacillus subtilis (one case), Streptococcus lactaceae (one case) and an unknown agent (one case); port removal was necessary in six of eight cases. The total cost per patient treated for a six-month period, consisting of the costs of purchase and implantation, treatment of early and late complications, and of maintenance of the device, is US$1,970. CONCLUSIONS: This study represents the largest published series of patients with totally implantable access ports connected to a Groshong catheter. We have shown that US$2,000 are sufficient to cover six months of chemotherapy in one patient using the most expensive commercially available implantable port. According to the present study, totally implantable access ports connected to a Groshong catheter are associated with high purchase and insertion costs, a low complication rate and low maintenance costs. These data support their increasing use in current oncologic medical practice.

Adolescent↗
PubMed1998

New treatments for breast cancer: breakthroughs for patient care or just steps in the right direction?

Three areas of clinical research in breast cancer treatment led to news breaking presentations at the American Society of Clinical Oncology (ASCO) meeting, 1998, in Los Angeles. All three subjects represent important advances in cancer medicine. PREVENTION: Two related drugs, tamoxifen and raloxifene, were found in placebo controlled trials to significantly reduce the incidence of breast cancer for women at increased risk of developing the disease. Patterns of relapse showed that the reduced rate of breast cancer was exclusively observed for tumors expressing estrogen receptors, while the rate of tumors classified as estrogen-receptor negative was similar for the treatment and the control groups. This may indicate that the observed reduction in breast cancer incidence is due to a treatment effect on occult disease rather than its prevention. We certainly have no adequate information on mortality prevention. ADJUVANT THERAPIES: Taxol given every three weeks for four courses following an adjuvant treatment with four courses of doxorubicin and cyclophosphamide (AC) combination was found to be superior to not adding treatment after the four courses of AC in a trial involving 3170 patients. At 22 months of median follow-up, the quoted P-values were P = 0.0077 for disease-free survival and P = 0.039 for overall survival, but these did not cross the prospectively defined interim analysis boundaries for statistical significance at the 0.05 level. The difference was observed early during follow-up, and was exclusively seen in the 40% of patients who had ER-negative primaries and, therefore, did not receive tamoxifen following chemotherapy. One may thus argue that the early difference observed was primarily due to differences in the duration of the treatment regimens in the two groups and the early entry into the trial of patients with particularly aggressive neoplasia (e.g., ER-negative primaries) who would have benefited from a longer duration treatment. TREATMENT OF ADVANCED DISEASE: The use of monoclonal antibodies to c-erb-B2 was found to induce responses in metastatic breast cancer. Patients with tumors expressing c-erb-B2 responded to weekly infusions of this biological agent. It was particularly impressive that the response rate for patients receiving infusion of the monoclonal antibodies together with the cytotoxics was superior to that with chemotherapy alone in a randomized trial. It is important to note that only patients with tumors overexpressing c-erbB-2 (the overall incidence is about 20%) were tested. It must still be demonstrated that the effect of these monoclonal antibodies is indeed confined to cells overexpressing c-erbB-2. Treatment related cardiac toxicity remains a problem, and the effects of treatment in various subsets of patients need to be defined before starting investigations in the adjuvant setting, which is a clear further objective of this specific research. The significant findings from clinical research opened several new questions, which must be answered before allowing them to be employed in routine patient care.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Factors affecting baseline quality of life in two international adjuvant breast cancer trials. International Breast Cancer Study Group (IBCSG).

Quality of life (QL) is used to assess treatments in clinical trials but may be influenced by other factors. We analysed the impact of biomedical, sociodemographic and cultural factors on baseline QL indicators in two International Breast Cancer Study Group trials. Patients with stage II breast cancer were randomized within 6 weeks of primary surgery to various adjuvant treatments. They were asked to assess five indicators of QL at baseline. QL forms were available for 1231 (83%) of the 1475 premenopausal and 989 (82%) of the 1212 post-menopausal patients, who were from nine countries and spoke seven languages. Culture (defined as language/country groups) had a statistically significant impact on baseline QL measures. Premenopausal patients with poor prognostic factors showed a tendency to report worse QL, with oestrogen receptor status as an independent predictor for mood (P = 0.0005). Older post-menopausal patients reported better emotional wellbeing (P = 0.002), mood (P = 0.002), and less effort to cope (P = 0.0009) compared with younger post-menopausal patients. Co-morbidity, type of surgery, treatment assignment and sociodemographic factors showed a statistically significant impact in post-menopausal patients only. Cultural and biomedical factors influenced baseline QL and should be considered when evaluating the impact of treatment on QL in international breast cancer clinical trials.

Adult↗
PubMed1998

Adjuvant chemoendocrine therapy in postmenopausal breast cancer: cyclophosphamide, methotrexate, and fluorouracil dose and schedule may make a difference. International Breast Cancer Study Group.

PURPOSE: Adjuvant cytotoxics prolong disease-free survival (DFS) and overall survival (OS) in patients with operable breast cancer. The first reported effective adjuvant combination regimen consisted of oral cyclophosphamide on days 1 to 14 with intravenous methotrexate and fluorouracil on days 1 and 8, repeated every 28 days (classical CMF). These drugs have since been extensively used with or without endocrine therapies and/or other cytotoxic agents. Although doses and schedules have varied widely, the combination of these three drugs is generically referred to as CMF. RESULTS: Reducing the dose and/or altering the schedule of CMF have compromised its efficacy in metastatic breast cancer. Reduction below standard dose of a similar regimen also gave inferior results in the adjuvant setting. CONCLUSION: Details of dose and schedule may therefore explain part of the heterogeneity of results observed with CMF. Particular controversy surrounds the contribution of CMF in postmenopausal women who are also receiving tamoxifen (TAM). However, the trials that demonstrated a significant benefit for the addition of CMF to TAM, even in postmenopausal women with estrogen receptor-positive tumors, used classical CMF. Therefore, adherence to the classical dose and schedule is recommended when CMF is used in adjuvant therapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Quality-of-life-adjusted survival analysis of interferon alfa-2b treatment for advanced follicular lymphoma: an aid to clinical decision making.

PURPOSE: To evaluate the trade-off of toxicity versus improved clinical outcome with interferon alfa-2b (IFN) administered concomitantly with a doxorubicin-containing regimen for the treatment of advanced follicular lymphoma. PATIENTS AND METHODS: A quality-of-life-adjusted survival analysis (Quality-Adjusted Time Without Symptoms or Toxicity [Q-TWiST]) was applied to the Groupe d'Etude des Lymphomes Folliculaires (GELF) trial 86, which compared a regimen of cyclophosphamide, doxorubicin, teniposide, and prednisone (CHVP) versus CHVP plus IFN in 242 patients with confirmed follicular lymphoma. CHVP was administered monthly for 6 months then every other month for 12 months. The IFN dosage was 5 x 10(6) U three times weekly for 18 months. RESULTS: After a median follow-up duration of 72 months, the IFN group gained a mean of 12.3 months of progression-free survival (PFS) and 7.4 months of overall survival (OS), but also experienced additional time with grade 3 or worse toxicity compared with the CHVP group. Sensitivity analysis demonstrated that CHVP plus IFN provided a greater amount of quality-adjusted survival regardless of the relative quality-of-life valuations placed on time with toxicity due to CVHP alone, time with toxicity due to CHVP plus IFN, and time following disease progression. This gain was significant (P < .05) in all cases except for patients who consider time with toxicity to have a low relative value and time following disease progression to have a high relative value. CONCLUSION: In patients with advanced follicular lymphoma, the clinical benefits of concomitant IFN can significantly offset the associated grade 3 or worse toxic effects. The magnitude of this clinical benefit depends on an individual patient's relative quality-of-life valuations for time with toxicity and time following disease progression.

Adult↗
PubMed1998

Intracavitary chemotherapy with thiotepa in malignant pericardial effusions: an active and well-tolerated regimen.

PURPOSE: Malignant pericardial effusion, although highly variable, is an uncommon complication of cancer. It is often associated with symptoms like dyspnea, chest pain, and cough, which may be severe and disabling. We analyzed the results of our current treatment policy to evaluate the effectiveness and tolerance of a new approach for this disorder. PATIENTS AND METHODS: Patients with malignant pericardial effusions were treated with intracavitary thiotepa (15 mg on days 1, 3, and 5) through an indwelling pericardial cannula after extraction of as much pericardial fluid as possible on day 0. Responses were assessed by clinical examination, computed tomographic (CT) scan, and echocardiography before treatment, 1 month after treatment, and every 2 months thereafter. Twenty-three patients with malignant symptomatic pericardial effusion were treated and all were assessable for effectiveness and tolerance of the procedure. RESULTS: Nine patients with breast cancer, 11 with lung cancer, two with an unknown primary tumor, and one with metastatic melanoma were treated. In all but three patients, systemic medical treatment was started after completion of intracavitary therapy. Nineteen patients responded to treatment (83%; 95% confidence interval, 61% to 95%) with a rapid improvement of symptoms. The median time to pericardial effusion progression was 8.9 months (range, 1 to 26). No significant side effects were registered, except one patient who had transient grade III thrombocytopenia and leukopenia and one patient who had grade I leukopenia. CONCLUSION: A short course of intracavitary treatment with thiotepa is highly effective and well tolerated in the treatment of malignant pericardial effusion.

Adult↗
PubMed1998

Practical considerations in the treatment of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) represents one of the most common neoplasms worldwide. To date, curative treatment options include liver transplantation or resection. Unfortunately, most patients are detected with nonresectable or -transplantable HCC due to disease extension or comorbid factors, and are therefore candidates only for palliative treatments. Palliative medical treatments, including systemic chemotherapy, immunotherapy or hormonal manipulation, have a borderline activity on HCC and cannot be recommended outside clinical trials. A high response rate has been reported with local therapies such as transcatheter arterial embolisation, intra-arterial chemotherapy or percutaneous alcohol (ethanol) injection, but as there is no clear evidence of a survival advantage for these treatment modalities, further investigations are required. Multidisciplinary treatment, including preoperative cytoreduction or postoperative adjuvant therapy, is currently under investigation, with encouraging survival results. HCC patients should be evaluated within clinical trials, possibly randomised and with homogeneous prognostic factors, in order that we may find the answer to all these important questions.

Carcinoma, Hepatocellular↗
PubMed1997

Formestane versus megestrol acetate in postmenopausal breast cancer patients after failure of tamoxifen: a phase III prospective randomised cross over trial of second-line hormonal treatment (SAKK 20/90). Swiss Group for Clinical Cancer Research (SAKK)

The aim of the study was to compare efficacy and tolerability of the new aromatase inhibitor formestane (Lentaron) with megestrol acetate (Megestat) (MGA) in postmenopausal patients with advanced breast cancer. 179 patients were randomised to receive either 250 mg formestane intramuscularly biweekly or MGA 160 mg orally daily. 51% of the patients had received tamoxifen as adjuvant treatment; 73% of the patients had positive and 16% unknown oestrogen receptor values. The response rate was 17% in both treatment arms (95% confidence interval 10-26% for formestane and 10-27% for MGA). Disease stabilisation > or = 6 months was seen in 25% of the formestane and 22% of the MGA patients. Time to treatment failure was 120 days in the formestane arm and 111 days in the MGA arm. There was no significant difference between the treatments with regard to response rate and time to treatment failure. Overall toxicity was similar in both arms, but weight gain > 3 kg (P = 0.081) and severe cardiovascular toxicity (P = 0.044) were more frequently observed with MGA, e.g. deep vein thrombosis 0/90 formestane versus 5/81 MGA cases (P = 0.022). Formestane was associated with worsening of hot flushes/sleeping problems (P = 0.051) and mild leucopenia (P = 0.004). In our study, formestane and MGA showed similar antineoplastic activity as second-line hormonal treatment for advanced breast cancer. Both drugs have a specific toxicity profile. MGA was associated with significantly more severe cardiovascular toxicity and weight increase than formestane.

Adult↗
PubMed1997

Retreating recurrent breast cancer with the same CMF-containing regimen used as adjuvant therapy. The International Breast Cancer Study Group.

Breast cancer metastases appearing soon after adjuvant chemotherapy (within 12 months of its completion) are usually resistant to retreatment with the same cytotoxic agents, while relapses occurring later (beyond 12 months) regress when rechallenged with the same agents, showing similar response rates observed in non-pretreated patients with advanced disease. The International Breast Cancer Study Group (IBCSG) prospectively explored the efficacy of retreatment for patients upon relapse using the same therapy administered during the adjuvant programme. 87 patients previously treated with an adjuvant CMF (cyclophosphamide, methotrexate, 5-fluorouracil) combination chemotherapy (with or without the addition of low-dose prednisone and tamoxifen), who had measurable first breast cancer relapse, usually after at least 6 months of completion of the adjuvant treatment, were treated with CMF. Pretreatment consisted of 1-3 CMF courses in 27 patients and 4 or more courses in 60 patients. 17 patients were retreated with additional tamoxifen or had tamoxifen stopped at relapse. The data of these patients are shown separately. 47 of the 86 fully evaluable patients (55%) had an objective response, which was complete in 25 (29%). The dominant metastatic type and the number of involved sites were the most important factors influencing response to retreatment. Patients with soft tissue metastases had a high response rate (36/52, 69%) compared with those who had visceral involvement (9/24, 38%) or those with bony disease (2/10, 20%) (P = 0.002). In conclusion, response rates to retreatment with CMF were similar to those expected in a non-pretreated population. The patterns of relapse and the number of metastatic sites were the most important factors predicting response to retreatment, while treatment-free interval (usually longer than 6 months due to the study design) did not influence response rates. This study supports the hypothetic effectiveness of late reintroduction of adjuvant cytotoxic therapy (prior to evidence of systemic relapse), upon which several current trials are based.

Adult↗
PubMed1997

Phase I-II study of vinorelbine in combination with 5-fluorouracil and folinic acid as first-line chemotherapy in metastatic breast cancer: a regimen with a low subjective toxic burden.

BACKGROUND: Vinorelbine, is an active drug in the treatment of metastatic breast cancer and has a favorable toxicity profile. Its combination with other effective and well-tolerated cytotoxics may thus be beneficial. We investigated the therapeutic effect of a combination of vinorelbine plus 5-fluorouracil and folinic acid as first-line treatment in patients with metastatic breast cancer. PATIENTS AND METHODS: Forty-five patients with advanced or metastatic breast cancer were enrolled in this phase I-II study and treated with 5-fluorouracil (350 mg/m2 i.v. on day 1 to 3), folinic acid (100 mg/m2 i.v. on day 1 to 3) and vinorelbine given on days 1 and 3 at the dose of 25 mg/m2 (dose level 1), or 30 mg/m2 (dose level 2). Therapy was given on an outpatient basis every three weeks. RESULTS: Phase I: Dose limiting toxicity (DLT) occurred at the second dose level of vinorelbine (30 mg/m2), with two out of three patients developing severe constipation ('ileus-like syndrome' grade 4), and fever (grade 2). Consequently, the dose evaluated in the phase II study was 25 mg/m2. Phase II: Objective responses were observed in 24 of 39 evaluable patients (95% confidence interval (95% CI), 47% to 77%). There were seven complete responses (18%), 17 partial responses (44%), and for nine patients (23%) disease was stable. Only six patients (15%) experienced disease progression. The median response duration was 10 months (range 6 to 24+) and the median time to progression was eight months (range 2 to 24+). Granulocytopenia was the most frequently observed side effect, with a grade 4 nadir being observed in 30 patients (77%), with four hospital admissions due to febrile neutropenia. Nausea, vomiting, and anorexia were mild to moderate and reported by less than half of the patients. Alopecia was moderate and occurred in about one-third of the patients. The other side effects were mild and easily manageable. CONCLUSIONS: This effective combination chemotherapy of vinorelbine, 5-fluorouracil and folinic acid is comparable to other first-line regimens in terms of efficacy, and is subjectively well tolerated, thus deserving a test in randomized trials in the advanced and adjuvant settings.

Adult↗
PubMed1997

Dose-finding study of paclitaxel and cyclophosphamide in advanced breast cancer.

BACKGROUND: The toxicity profile of prolonged infusions of paclitaxel in combination with cyclophosphamide in metastatic breast cancer has already been defined. The objective of this dose-finding study was to determine the maximum tolerable doses (MTDs) of shorter (three-hour) infusions of paclitaxel in combination with i.v. bolus cyclophosphamide in patients who had previously received a maximum of one chemotherapy for advanced breast carcinoma. The MTD of the same regimen with granulocyte colony-stimulating factor (G-CSF) support was then established. PATIENTS AND METHODS: Eighty women with metastatic breast cancer received a total of 352 fully evaluable courses of therapy. The starting doses were paclitaxel 135 mg/m2 and cyclophosphamide 750 mg/m2 given every three weeks. At least three patients were treated at each dose level and if there were dose-limiting toxic effects during the first cycles three additional patients were entered. G-CSF support (5 micrograms/kg s.c.) was added to the second cycle if specific dose-limiting toxicities had occurred during the first cycle. The MTD was defined as the dose level at which more than two of six patients presented dose-limiting toxicities during the first cycle. RESULT: Febrile neutropenia (n = 4) and severe thrombocytopenia (n = 1) defined the MTDs of paclitaxel as 200 mg/ m2 and of cyclophosphamide as 2,000 mg/m2 with or without G-CSF in patients with and, respectively, without prior chemotherapy for advanced disease. Non-hematologic toxicity was moderate. Recommended doses were 200 mg/m2 of paclitaxel and 1,750 mg/m2 of cyclophosphamide with or without G-CSF in patients with and, respectively, without prior chemotherapy. The overall response rate was 25% and 50%, respectively, in patients with and without prior chemotherapy for metastatic disease. Complete remissions (9%) were reported only in patients without prior chemotherapy; antitumour activity in women with anthracycline-resistant disease, with an 8% response rate (95% CI: 1%-26%), was poor. CONCLUSIONS: Paclitaxel at 200 mg/m2 and cyclophosphamide at 1,750 mg/m2 can be safely administered every three weeks to women with advanced breast cancer. The moderate antitumour activity observed with the schedule tested argues against its use as initial therapy for advanced breast cancer.

Adult↗
PubMed1997

Menstrual cycle and timing of breast surgery in premenopausal node-positive breast cancer: results of the International Breast Cancer Study Group (IBCSG) Trial VI.

PURPOSE: It has been postulated that breast cancer surgery performed during the follicular phase of the menstrual cycle is associated with poorer outcome. PATIENTS AND METHODS: We tested this hypothesis by evaluating disease-free survival (DFS) for 1033 premenopausal patients who received definitive surgery either during the follicular phase (n = 358) or the luteal phase (n = 675). All patients were enrolled in a randomized trial conducted between July 1986 and April 1993. All had node positive breast cancer and randomization was stratified by estrogen receptor (ER) status. All patients received at least three cycles of adjuvant cyclophosphamide, methotrexate, and 5-fluorouracil (CMF). The median follow-up was 60 months. RESULTS: Patients who underwent definitive surgery for breast cancer in the follicular phase had a slightly worse disease-free survival than those operated on during the luteal phase (five-year DFS percentage: 53% versus 58%; hazard ratio, 1.13; 95% confidence interval (CI), 0.94-1.38; P = 0.20). The effect was significantly greater for the subpopulation of 300 patients with ER-negative primaries (P = 0.02 interaction effect; five-year DFS percentages 42% vs. 59%; hazard ratio 1.60; 95% CI, 1.12-2.25; P = 0.008). The effect of timing of surgery diminished for analyses based on lesser surgical procedures, e.g., excisional biopsies. In particular, no effect of timing was observed for fine needle aspiration procedures. CONCLUSIONS: Surgical procedures which are more extensive than a fine needle aspiration biopsy might be associated with worse prognosis if conducted during the follicular phase of the menstrual cycle. This phenomenon was seen predominantly for high risk breast cancer with low levels or no estrogen receptors in the primary tumor.

Breast Neoplasms↗
PubMed1997

Quality of life assessment in patients receiving adjuvant therapy for breast cancer: the IBCSG approach. The International Breast Cancer Study Group.

BACKGROUND AND PURPOSE: The International Breast Cancer Study Group (IBCSG) has developed and approach for assessing the impact of adjuvant therapy on quality of life (QL) within the framework of international, multilingual clinical trials. The major steps are summarized. Conceptual, methodological and practical issues are discussed with reference to results of two trials closed to accrual (IBCSG VI, VII) and one subsequent ongoing trial (IBCSG IX). PATIENTS AND METHODS: QL was assessed in pre- and post-menopausal patients with operable breast cancer. Various single-item linear analogue self-assessment (LASA) scales were used as indicators of components of QL, including global indicators of well-being, functioning and health perception, and specific indicators of symptoms of disease and treatment. In trials VI and VII, QL was assessed at baseline, during adjuvant treatment and follow-up, and at recurrence. Based on this experience, the QL form was revised for subsequent trials and further investigated in a subsample of patients randomized into trial IX. RESULTS: In trials VI and VII, the QL indicators were responsive to the impact of biomedical factors at baseline, various adjuvant treatments, changes over the first 18 months, and recurrence. In trial IX, the revised QL form was well accepted by patients and staff. Completing this form did not exceed five minutes. QL differences between on and off cytotoxic treatment strengthen the claim that these measures are responsive. Correlations and logistic regression analyses show the expected relationship among the various global and specific indicators. CONCLUSION: Results from two trials closed to accrual and an ongoing trial confirm the feasibility, validity and clinical relevance of the IBCSG approach for studying the impact of adjuvant breast cancer therapy on QL in international clinical trials.

Breast Neoplasms↗
PubMed1997

High-dose chemotherapy with autologous stem cell transplantation is feasible and safe in a regional hospital. A 6-year experience in southern Switzerland.

High-dose therapy with bone marrow (BM) or blood stem cell (BSC) support is a high-technology technique usually administered in specialized tertiary centers. The use of BSC has made this technique simpler and accessible also to smaller hospitals. We retrospectively analyzed the data of patients with lymphoma, leukemia and other tumors who received high-dose therapy and BM or BSC transplantation in our district hospital, looking at the type of procedure performed, complications, use of growth factors, and progression-free and overall survival. A total of 40 patients were transplanted over 6 years. No procedure-related deaths and no permanent organ toxicities were seen. The use of BSC brought about a great reduction in the duration of hospital stay, septic complications and transfusion of blood components. For patients with lymphoma (n = 20) the probabilities of progression-free survival and of overall survival at 2 years are 48% (95% C.I. 28-68%) and 68% (95% C.I. 46-84%), respectively. Based on these data, we believe that ABMT and BSC transplantation are feasible and safe in a peripheral hospital when the appropriate human and technical conditions are present. Treatment outcome is then comparable to that of specialized centers.

Adolescent↗
PubMed1997

Prognostic importance of thymidylate synthase expression in early breast cancer.

PURPOSE: To assess the prognostic importance of thymidylate synthase (TS) expression in breast tumors of patients with early-stage breast cancer, and to determine whether the benefit of chemotherapy (CT) is associated with TS expression. PATIENTS AND METHODS: The level of TS expression was evaluated in 210 node-negative and 278 node-positive patients enrolled onto Trial V of the International Breast Cancer Study Group ([IBCSG] formerly the Ludwig Breast Cancer Study Group) with a median follow-up time of 8.5 years. TS expression was assessed using the immunohistochemical method with the monoclonal antibody TS 106 on paraffin-embedded tissue specimens. RESULTS: High TS expression was associated with a significantly worse prognosis in node-positive but not in node-negative breast cancer patients. Twenty-seven percent of node-positive patients with high TS expression were disease-free at 10 years, compared with 44% of node-positive patients with low TS expression (P = .03). Forty-one percent of patients with node-positive high-TS-expressing tumors were alive after 10 years, compared with 49% of those with low TS expression (P = .06). The association between TS and disease-free survival (DFS) and overall survival (OS) was independent of other prognostic factors such as tumor size, tumor grade, nodal status, vessel invasion, estrogen receptor (ER)/ progestin receptor (PR) status, c-erb B-2, or Ki-67 expression. In node-positive patients, six cycles of standard adjuvant cyclophosphamide, methotrexate, and fluorouracil ([5-FU] CMF) CT improved DFS and OS compared with one cycle of perioperative CMF therapy. The magnitude of this benefit was greatest in patients whose tumors had high TS expression (P < .01 for DFS; P < .01 for OS). Node-negative patients demonstrated no difference in outcome to CT based on TS expression; however, the power to detect differences was limited by the small number of events in this group. CONCLUSION: In early-stage breast cancer, high TS expression is associated with a significantly worse prognosis in node-positive patients. Node-positive patients with high TS levels demonstrate the most significant improvement in DFS and OS when treated with six cycles of conventional adjuvant CMF therapy.

Antineoplastic Combined Chemotherapy Protocols↗