Search PubMed⌕ Search

Biomedical subjects

A Goldhirsch

Publications and source records attributed to A Goldhirsch.

At least 145 records · Page 8Linked to original sources
PubMed1997

Overview of randomized perioperative polychemotherapy trials in women with early-stage breast cancer.

PURPOSE: To determine whether perioperative polychemotherapy (PeCT) can significantly prolong the overall survival of women with early-stage breast cancer. METHODS: A meta-analysis that used updated individual patient data from all available randomized trials of PeCT, both published and unpublished, was conducted. Data on 6,093 patients (1,124 deaths and 1,912 recurrences) from five clinical trials were available (median follow-up duration, 5.3 years; maximum, 11.3 years). RESULTS: No significant effect of PeCT on overall survival was observed. However, patients who received PeCT had a significantly longer disease-free survival (hazards ratio [HR], 0.89; 95% confidence interval [CI], 0.82 to 0.98; P = .02). Time to local recurrence was significantly prolonged in the PeCT arm (HR, 0.68; 95% CI, 0.58 to 0.80; P < .0001). Likewise, there was a borderline significant difference in favor of PeCT in terms of time to distant metastases (HR, 0.90; 95% CI, 0.81 to 1.00; P = .05). Subgroup analyses suggest that node-negative women benefited the most from treatment. CONCLUSION: At present, there is no evidence that PeCT is able to prolong overall survival in patients with early-stage breast cancer; however, further follow-up evaluation is required. PeCT significantly prolongs disease-free survival, especially in node-negative women, which emphasizes once more the need for clinical trials in this subgroup.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

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↗
PubMed1996

A quality-adjusted time without symptoms or toxicity (Q-TWiST) analysis of adjuvant radiation therapy and chemotherapy for resectable rectal cancer.

BACKGROUND: Combined radiation therapy and chemotherapy after surgery, compared with postsurgical radiation therapy alone, has been shown to improve disease-free survival and overall survival significantly among patients with poor-prognosis (i.e., advanced stage disease or metastasis to regional lymph nodes) resectable rectal cancer. However, the combined therapy is associated with more toxic effects, raising the question of whether the benefits of the treatment justify its quality-of-life costs for the individual patient. PURPOSE: To assess the trade-offs between improved survival and increased treatment toxicity, we reanalyzed data from a randomized clinical trial that compared the efficacy of combined adjuvant chemotherapy and radiation therapy with adjuvant radiation therapy alone in the treatment of patients with poor-prognosis resectable rectal cancer. METHODS: The data were from a North Central Cancer Treatment Group trial in which 204 patients with poor-prognosis rectal cancer were randomly assigned to receive either postoperative radiation therapy alone or radiation therapy plus fluorouracil-based chemotherapy. A quality-adjusted time without symptoms or toxicity (Q-TWiST) analysis was used to account for freedom from symptomatic disease and from early and late side effects of treatment. All reported P values are two-sided. RESULTS: As reported previously, the combined therapy reduced the risk of relapse by 34% (95% confidence interval [CI] = 12%-50%; P = .0016) and reduced the overall death rate by 29% (95% CI = 7%-45%; P = .025) in comparison with adjuvant radiation therapy alone. In the 5 years following assignment to treatment, patients who received the combined therapy had more time with toxicity (3.1 months; 95% CI = 2.0-4.1 months), shorter survival after relapse (3.6 months less; 95% CI = 0.9-6.3 months less), and more TWiST (6.1 months; 95% CI = 0.2-12.0 months) than patients who received adjuvant radiation therapy alone. Despite an increase in the amount of time that individuals spent with early and late toxic effects, the Q-TWiST analysis indicated that the combined therapy conferred significantly greater benefit for a wide range of patient preferences about living with the toxicity of treatment or the symptoms of overt disease. CONCLUSIONS AND IMPLICATIONS: Use of combined chemotherapy and radiation therapy as an adjuvant to surgery for patients with poor-prognosis resectable rectal cancer is justified, since the improved outcome in terms of delayed recurrence and increased survival balances the time spent with early and late toxic effects. The Q-TWiST method is an excellent way to compare treatment outcomes that include quality-of-life considerations.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

Timing of radiotherapy and chemotherapy following breast-conserving surgery for patients with node-positive breast cancer. International Breast Cancer Study Group.

PURPOSE: A controversy exists regarding whether it is safe to delay radiation therapy until the completion of chemotherapy following breast-conserving surgery for patients with node-positive breast cancer. Within the context of two concurrent randomized clinical trials we had the opportunity to evaluate outcomes for patients who received breast irradiation after completing different durations of chemotherapy. METHODS AND MATERIALS: From July 1986 to April 1993 the International Breast Cancer Study Group (IBCSG) Trial VI randomly assigned 1554 pre/perimenopausal node-positive breast cancer patients to receive cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) for either three consecutive courses on months 1-3, or six consecutive courses on months 1-6, both with or without reintroduction CMF. IBCSG Trial VII randomly assigned 1266 postmenopausal node-positive breast cancer patients to receive tamoxifen for 5 years, or tamoxifen for 5 years with three early cycles of CMF, both with or without three courses of delayed CMF. Both trials allowed a choice of mastectomy, or breast-conserving surgery plus radiation therapy, and both were stratified by type of surgery. Radiotherapy was delayed until the initial block of CMF was completed; 4 or 7 months after surgery for pre/perimenopausal patients, and 2 or 4 months after surgery for postmenopausal patients. Over both trials, 718 eligible patients elected to receive breast-conserving surgery plus radiation therapy: 433 on Trial VI, and 285 on Trial VII. Four-year actuarial total failure rates (failure at any site), risks of developing distant metastases (DM at any time during observation), and overall survival (OS) were estimated using the Kaplan-Meier method. To avoid potential bias due to competing causes of failure, only patients who could be followed for at least 4 years (enrolled prior to July 1, 1990) were used to evaluate the patterns of first relapse site. Crude percents of local failure with or without other sites (LF), distant metastases including regional nodal failure (DM/RNF), or other first events (second primaries/death without recurrence) were estimated for each treatment group. For this report, an intent to treat analysis was performed at a median follow-up of 48 months. RESULTS: No differences were found in the 4-year actuarial total failure rates, risk of developing distant metastases, and overall survival among the two radiotherapy groups of each study. The cumulative incidence of types of first failure and the 4-year crude rates showed no treatment differences in the patterns of site of first event. Estimates for the 4-year crude percent of local failures were 8 and 9% for pre/perimenopausal patients who had radiation therapy at 4 or 7 months after surgery, and 3 and 6% for postmenopausal patients who had radiation therapy at 2 months or 4 months after surgery. CONCLUSIONS: For node positive patients receiving breast-conserving surgery followed by radiation therapy, the incidence of breast recurrence in the conserved ipsilateral breast within 4 years was between 8 and 9% for pre/perimenopausal patients and between 3 and 6% for postmenopausal patients. After 48 months of median follow-up, administering radiation therapy after three or six cycles of CMF for pre/perimenopausal women, or after no cycles or three cycles of CMF for postmenopausal women does not influence overall efficacy or local control in this series.

Adult↗
PubMed1996

Impact of adjuvant therapy on quality of life in women with node-positive operable breast cancer. International Breast Cancer Study Group.

BACKGROUND: Adjuvant therapy for early breast cancer is effective but may be toxic. Our aim was to investigate the impact of the presence, timing, and duration of adjuvant chemotherapy on patients' perceptions of their quality of life (QL). METHODS: International Breast Cancer Study Group trial VI assessed adjuvant chemotherapy in 1475 premenopausal and perimenopausal patients, and trial VII assessed adjuvant tamoxifen or chemoendocrine therapy in 1212 postmenopausal patients with node-positive breast cancer. Patients were asked to complete a QL questionnaire-single-item linear analogue self-assessment scales measured physical wellbeing, mood, appetite, and perceived adjustment/coping. QL was assessed in this way at the beginning of treatment, 2 months after the start of treatment, every 3 months, and at 1 and 6 months after recurrence. FINDINGS: Baseline QL scores decreased as the number of involved axillary nodes increased (for example, mean mood score: 66.1 for women with one positive node, 66.4 for two to four positive nodes, 61.3 for five to nine positive nodes, and 59.1 for ten or more positive nodes; p = 0.008 for trends), and were lower in patients with oestrogen-receptor-negative than in patients with oestrogen-receptor-positive tumours (61.4 vs 66.3, p = 0.0009). All treatment groups showed substantial improvement in QL scores during adjuvant therapy. Patterns of QL scores reflected presence, duration, and timing of cytotoxic treatment. Longer initial cytotoxic therapy delayed improvement in QL scores. Later cytotoxic therapy had transient adverse effects. Anticipation of future therapy also affected QL scores. INTERPRETATION: Overall, chemotherapy had a measurable adverse effect on QL, but this effect was transient and minor compared with patients' adaptation/coping after diagnosis and surgery. This finding should encourage patients and doctors to choose appropriate adjuvant therapy with less concern for initial toxicity.

Antineoplastic Agents, Hormonal↗
PubMed1996

Adjuvant chemotherapy plus tamoxifen compared with tamoxifen alone for postmenopausal breast cancer: meta-analysis of quality-adjusted survival.

BACKGROUND: Adjuvant tamoxifen for early breast cancer provides an improvement in relapse-free (RFS) and overall survival (OS), especially for older women. We carried out a meta-analysis to find out whether the benefit of adding chemotherapy to tamoxifen outweighs its costs in terms of toxic effects for postmenopausal patients. METHODS: The meta-analysis of quality-adjusted survival was based on data from 3920 patients aged 50 years or older with node-positive breast cancer randomly assigned in nine trials that compared combination chemotherapy plus tamoxifen with tamoxifen alone. The nine trials were included in the worldwide overview conducted by the early breast cancer trialists' collaborative group (EBCTCG). The quality-adjusted time without symptoms or toxicity (Q-TWiST) method was used to provide treatment comparisons incorporating differences in quality of life associated with subjective toxic effects of treatment and symptoms of disease relapse. FINDINGS: Within 7 years of follow-up the modest benefit of increased RFS and OS for patients who received chemotherapy just balanced the costs in terms of acute toxic side-effects. Chemotherapy-treated patients gained an average of 5.4 months of RFS and 2 months of OS (neither statistically significant), but had to receive cytotoxic treatment for between 2 and 24 months to achieve these gains. No values of preference weights for time spent undergoing chemotherapy and time after relapse gave significantly more Q-TWiST with chemotherapy plus tamoxifen than with tamoxifen alone. INTERPRETATION: Within 7 years of follow-up, adjuvant chemoendocrine therapy did not provide more quality-adjusted survival time than tamoxifen alone for women aged 50 years or older with node-positive breast cancer. Better selection and administration of chemotherapy regimen, different scheduling of chemotherapy and tamoxifen, and appropriate use of patient and tumour characteristics may increase the therapeutic advantage of the combination.

Antineoplastic Agents, Hormonal↗
PubMed1996

Treatment of ovarian cancer with surgery, short-course chemotherapy and whole abdominal radiation.

BACKGROUND: The primary aim was to induce a high number of pCR in early (FIGO IC, IIB + C) - and advanced (FIGO III-IV) - stage ovarian cancer with a surgery plus 4 cycles of cisplatin and melphalan (PAMP) regimen. The second objective was to prevent relapse with WAR in patients in remission after chemotherapy. PATIENTS AND METHODS: 218 eligible patients were treated after staging laparotomy with cisplatin 80 mg/sqm i.v. on day 1 and melphalan 12 mg/sqm i.v. on day 2 q 4 weeks. Response was verified by second-look laparotomy. WAR was carried out with the open field technique on a linear accelerator (daily dose: 1.3 Gy, total dose: 29.9 Gy) in patients with pathological or clinical CR or pathological PR with microscopical residual disease. RESULTS: 146/218 patients (67%, 95% CI: 61%-73%) responded to PAMP: 56 (26%) achieved pCR, 24 (11%), cCR, 56 (26%) pPR and 10 (5%) cPR (c = clinical, p = pathological). Multivariate analyses revealed that in advanced stages (92 cases in remission), the achievement of pCR was the most important factor for longer time to failure (TTF) and survival. Only 51/118 (43%) patients in remission received WAR. Early-stage patients <= 55 years were more likely to have WAR than patients older than 55 years (77% vs. 23%; p = 0.02). Advanced-stage patients with cCR were less likely to be irradiated than patients with pCR or pPR (10% vs. 51%; p = 0.003). Toxicity of PAMP was acceptable with 10% of WHO grade 4 hematologic toxicity. Acute hematological toxicity of WAR caused interruption (33%) or incompleteness (33%) of irradiation in the majority of patients. CONCLUSIONS: PAMP is an effective treatment for advanced ovarian cancer with a 67% response rate after 4 cycles. For the majority of patients in remission, WAR as a consolidation treatment was hardly feasible. For these patients new treatment modalities to consolidate remission are needed.

Adult↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

Paclitaxel induces significant changes in epidoxorubicin distribution in mice.

BACKGROUND: Inhibition of Pgp can affect the distribution and the pharmacokinetics of anthracyclines, causing marked changes in their toxicity. Since both paclitaxel and cremophor are substrates of Pgp, it was hypothesized that they could modify the pharmacokinetics of anthracyclines in a similar fashion. PURPOSE OF THE STUDY: To evaluate whether pretreatment of mice with cremophor or paclitaxel dissolved in cremophor could induce changes in the distribution of epidoxorubicin (EpiDx). MATERIALS AND METHODS: Male CDF1 mice were treated with ethanol or cremophor or paclitaxel and 30 min later with EpiDx (15 mg/kg i.v.). EpiDx serum and tissue levels were determined at several time points after EpiDx treatment by high pressure liquid chromotagraphy (HPLC) assay coupled with fluorimetric detection. RESULTS: Pretreatment with paclitaxel dissolved in cremophor induced a highly significant increase in EpiDx levels in all tissues examined including heart. At 8 h heart levels in mice treated with EpiDx alone, EpiDx and cremophor and EpiDx and paclitaxel were 8.3 micrograms/g, 10.9 micrograms/g and 16.7 micrograms/g (P < 0.01), respectively. Cremophor alone induced a similar increase in spleen EpiDx levels but had only a moderate effect on heart and lung EpiDx levels. Levels of doxorubicin (Dx) aglycone in kidney and liver of mice treated with paclitaxel and EpiDx were higher than those in mice treated with EpiDx alone. CONCLUSIONS: A pharmacokinetic interaction between paclitaxel and EpiDx was clearly demonstrated in mice. The much higher tissue levels of EpiDx after paclitaxel pretreatment may be the reason for the increased toxicity of EpiDx when administered soon after paclitaxel.

Animals↗
PubMed1996

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↗
PubMed1996

Responsiveness of a single-item indicator versus a multi-item scale: assessment of emotional well-being in an international adjuvant breast cancer trial.

A single-item linear analogue self-assessment scale for mood was compared with a 28-item adjective checklist for emotional well-being. To confirm its concurrent validity and responsiveness to treatment and recurrence in patients with breast cancer, emotional well-being was assessed every 3 months for 2 years and at 1 and 6 months after recurrence in 1,169 patients who were premenopausal and 960 patients who were postmenopausal. These patients were enrolled in two International Breast Cancer Study Group randomized clinical trials in operable breast cancer conducted from 1986 to 1993. To assess concurrent validity, Pearson's correlation between the linear analogue self-assessment scale and the adjective checklist were calculated for each time-point within each treatment group and for the two assessments after recurrence. Responsiveness to treatment and recurrence were analyzed using paired t tests and the squared ratio of these t tests, an estimate of relative efficiency. Concurrent validity of the mood linear analogue self-assessment was consistently confirmed across four language groups. Both measures were responsive; out of 24 changes over time, 19 were in the expected direction for the linear analogue self-assessment scale (p < or = 0.05 for 9 of 19) and 17 for the adjective checklist (p < or = 0.05 for 10 of 17). The linear analogue self-assessment scale was less but significantly efficient for detection of treatment effects, with relative efficiency estimates ranging from 0.16 to 2.45 and a median of 0.66 among the comparisons with relatively stable estimates (/t/ > or = 1.0) and more efficient for recurrence than the adjective checklist. The mood linear analogue self-assessment scale is a valid indicator of emotional well-being in patients with breast cancer in large multicenter, multicultural trials in which comprehensive scales are less feasible. This investigation supports the clinical relevance of linear analogue self-assessment scales as indicators of components of quality of life in cancer clinical trials.

Adult↗
PubMed1996

Quality-of-life-adjusted survival analysis of interferon alfa-2b adjuvant treatment of high-risk resected cutaneous melanoma: an Eastern Cooperative Oncology Group study.

PURPOSE: To evaluate the quality-of-life effects of adjuvant high-dose interferon alfa-2b (IFN alpha 2b) treatment of high-risk melanoma. PATIENTS AND METHODS: A quality-of-life-adjusted survival analysis (Quality-Adjusted Time Without Symptoms, and Toxicity [Q-TWiST]) was applied to the Eastern Cooperative Oncology Group Trial E1684, which compared high-dose IFN alpha 2b treatment for 1 year versus observation in 280 high-risk patients. IFN alpha 2b was administered at a dosage of 20 mU/m2 intravenously daily for 5 days per week for 4 weeks, and then three times weekly at 10 mU/m2 subcutaneously for 48 weeks. RESULTS: After 84 months of median follow-up time, the IFN alpha 2b group gained a mean of 8.9 months without disease relapse (P = .03) and 7.0 months of overall survival (P = .07) as compared with the observation group, but had severe treatment-related toxicity for 5.8 months, on average. The IFN alpha 2b group had more quality-of-life-adjusted time than the observation group regardless of the relative valuations placed on time with toxicity (Tox) and time with relapse (Rel). This gain was significant (P < .05) for patients who consider Tox to have a high relative value and Rel to have a low relative value. In contrast, for patients who value Tox about the same as Rel, the quality-adjusted gain for IFN alpha 2b was not statistically significant. An analysis stratified according to tumor burden indicated that the benefit of IFN alpha 2b was greatest in the node-positive strata. CONCLUSION: For patients with high-risk melanoma, the clinical benefits of high-dose IFN alpha 2b can offset the toxic effects. The optimal treatment for an individual patient depends on the patient's tumor burden and preferences regarding toxicity and disease relapse.

Antineoplastic Agents↗
PubMed1996

Endocrine therapies of breast cancer.

Endocrine therapies for breast cancer have been used for more than a century. The concept that changing the hormonal balance of the patient with breast cancer could lead to changes in tumor growth and regression of metastatic disease was recognized even before hormones and endocrine agents were available. Ablation of ovaries, adrenals, or hypophysis was used in advanced disease to obtain tumor regression and control of symptoms. Ovarian ablation was also tested for operable breast cancer showing a significant beneficial treatment effect. Several endocrine agents have been developed in recent years: estrogens, androgens, progestins, antiestrogens, aromatase inhibitors, gonadotropin-releasing hormone analogs, antiprogestins, and antiandrogens. The use of some of these agents in advanced disease led to investigations in early breast cancer: tamoxifen was the drug which was most extensively tested, showing a significant long-term benefit for treated patients. Progestins (medroxyprogesterone acetate) and aromatase inhibitors (aminoglutethimide) were also tested in a few clinical trials, but no conclusive recommendations for their use in patients with operable disease may be formulated. The most important current challenges for the appropriate use of endocrine therapies in breast cancer include (1) understanding the effect of endocrine therapies and the mechanisms of resistance associated with their use; (2) developing new agents with novel endocrine antitumor effect; (3) defining the best way to combine endocrine agents with cytotoxics or with other endocrine manipulations; and (4) identifying long-term effects of endocrine agents in terms of disease control and prevention, as well as desirable and undesirable side effects.

Aminoglutethimide↗