Neutrophil count is not associated with infection episodes in breast cancer patients treated with anthracycline-based chemotherapy

The aim was to evaluate the impact of anthracycline-based chemotherapy on neutrophil count and infections in breast cancer women. The medical records of patients were retrospectively and prospectively reviewed (8-year period). Patients were grouped according to anthracyclines at different doses: (1) Scheme 1 ( n  = 56, 224 courses): 50–60 mg/m²; and (2) Scheme 2 ( n  = 25, 100 courses): 65–75 mg/m², associated to cyclophosphamide and 5-fluorouracil, at 21-day intervals between courses. Neutrophil count was performed on diagnosis and 48–72 h before each chemotherapy course. Patients were followed up for neutrophil count and infection episodes for three consecutive courses. Multivariate analysis was used to determine independent factors for infection. After the first course, neutrophil count was reduced than baseline ( P  < 0.001) and maintained during the subsequent courses, without differences between courses or groups. There were 49 infection episodes (63.2% urinary, 18.4% neutropenic fever and 18.4% diverses), mainly between course 1–2 (39%) and course 3–4 (38%) of chemotherapy. Patients evaluated as presenting or not with infection episodes did not differ in neutrophil count. The number of chemotherapy courses ( P  < 0.05), but not age, neutrophil count or chemotherapy regimen, was associated with infection. We concluded that progressive chemotherapy, but not neutrophil count, was an independent factor for infection.     

Docetaxel in combination with 5-fluorouracil in patients with metastatic breast cancer previously treated with anthracycline-based chemotherapy: a phase I, dose-finding study

This phase I study evaluated the maximum tolerated dose, dose-limiting toxicity and recommended dose of docetaxel in combination with 5-fluorouracil (5-FU) in patients with metastatic breast cancer previously treated with anthracycline-based chemotherapy. 32 patients received docetaxel at 60, 75, 85 or 100 mg/m(2) by 1-h intravenous (i.v.) infusion, followed, after a 1-h interval, by 5-FU at 250, 350, 500 or 750 mg/m(2)/day by continuous infusion over 5 days every 3 weeks. Dose-limiting stomatitis defined the maximum tolerated dose at a docetaxel dose of 100 mg/m(2) with 5-FU 750 mg/m(2)/day. None of 5 patients treated at the previous dose level (docetaxel 85 mg/m(2) with 5-FU 750 mg/m(2)/day) had a dose-limiting toxicity in the first cycle, and this was, therefore, considered the recommended dose. The combination was generally well tolerated. Grade 4 neutropenia was common (29 patients; 91%), but no patient experienced febrile neutropenia of duration >3 days requiring i.v. antibiotics. An objective response was achieved by 18 patients overall (56%), and in 4 out of 5 patients treated with the determined recommended dose. No pharmacokinetic interaction between docetaxel and 5-fluorouracil was apparent. The activity of docetaxel 85 mg/m(2) with 5-fluorouracil 750 mg/m(2)/day will be explored more extensively in phase II studies of patients with metastatic breast cancer previously treated with anthracycline-based chemotherapy.     

蒽环类药物对乳腺癌患者月经状态的影响

目的研究乳腺癌患者年龄及不同蒽环类化疗药物对化疗诱导停经的影响,为临床合理用药提供依据。方法前瞻性研究绝经前乳腺癌患者接受化疗后月经变化情况,比较不同年龄段及使用不同化疗药物的患者月经状态变化的差异。结果137例乳腺癌患者,化疗致闭经（CIA）的发生率为73．72％（101／137）,长期闭经（LCIA）发生率为43．80％（60／137）。40岁以下患者CIA和LCIA的发生率均显著低于40岁以上的患者（X^2=25．32、18．42,P〈0．05）,并且40岁以下组发生CIA后月经恢复率为61．90％（13／21）,明显高于40岁以上组的35．00％（28／80）,差异有统计学意义（X^2=4．99,P=0．025）。40岁以上患者中表柔比星（商品名：法玛新）、表柔比星（商品名：艾达生）、吡柔比星诱导LCIA率差异有统计学意义（X^2=6．92,P=0．031）。结论年龄是CIA的重要因素,40岁以下患者月经受化疗影响较小,停经多为可逆性。40岁以上患者使用不同的蒽环类化疗药物对月经状态的影响差异有统计学意义。     

Long-term survival of patients treated with combination chemotherapy for metastatic breast cancer

Long-term survival of patients with metastatic breast cancer treated on two prospective stratified randomised trials has been analysed. Patients on study B122 received either cyclophosphamide, methotrexate and 5-fluorouracil (CMF) or cyclophosphamide, doxorubicin and 5-fluorouracil (CAF). On study B141 patients received CAF or mitolactol (dibromodulcitol), doxorubicin and vincristine alternating after every three cycles with three cycles of CMF (DAV/CMF). Long-term follow-up of 172 patients showed no significant survival difference (in multivariate regression models) for treatment with either CMF vs. CAF vs. DAV/CMF. The difference in median survival times between CMF and CAF showed a trend in favour of CAF. Advances in the management of metastatic breast cancer in postmenopausal women obtained by doxorubicin regimens have had a small but measurable impact on survival, but known patient discriminants were not overridden by the treatment regimens investigated in these studies.     

Optimum anthracycline-based chemotherapy for early breast cancer

Adjuvant chemotherapy improves the overall survival of women treated after surgery for early breast cancer. Several trials have suggested that anthracycline-containing regimens are more effective than those that do not contain anthracyclines. A modest overall benefit has also been confirmed by the Early Breast Cancer Trialists' Collaborative Group overview. Newer agents, such as the taxanes, are now being tested in the adjuvant setting in randomised trials. The control group of such studies should receive the optimum standard treatment. There are several anthracycline-based regimens in common use, varying in terms of the type of anthracycline used, the dose, and drug scheduling. We review the available evidence and consider whether the optimum anthracycline-containing chemotherapy schedule has now been identified.     

Clinical course of breast cancer patients with osseous metastasis treated with combination chemotherapy

Between July 1973 and December 1979, 1171 patients with metastatic breast cancer were treated with doxorubicin-containing chemotherapy. Of those patients, 195 had osseous metastases only. Upon initial diagnosis, 48% had osteolytic metastases; 13% had osteoblastic metastases; 38% had mixed metastases; and 1% had diffuse osteoporosis without any obvious bone destruction. The most common sites of involvement were the dorsal spine (62%), lumbosacral spine (72%), and pelvis (79%). Objective response to chemotherapy was observed in 59% of patients; complete responses were noted in 7%, and partial responses in 52%. The median survival was 28 months (range, 1-118 months). The median time lapse between the start of chemotherapy and disease progression was 14 months (range, 1-109 months). In 32 patients who responded to the treatment, chemotherapy was discontinued after 2 years, and their median duration of continued remission at 39 and 75 months after the completion of therapy. The incidence of pathological fractures was 57%; the most common sites were the spine, which sustained compression fractures, and the ribs. The incidences of hypercalcemia and spinal cord compression due to metastases were 19% and 10%, respectively.     

Intima-media thickness,myocardial perfusion and laboratory risk factors of atherosclerosis in patients with breast cancer treated with anthracycline-based chemotherapy

An increased incidence of complications of atherosclerosis has been noted in cancer survivors. The aim of the present study was to evaluate, in patients with breast carcinoma, the effect of antracycline-based chemotherapy on carotid intima-media thickness (IMT), myocardial perfusion, assessed by single-photon emission tomography (SPECT) and laboratory parameters associated with the risk of atherosclerosis. Thirty-six patients with breast cancer were evaluated before and after anthracycline-based chemotherapy. Retinol, alpha-tocopherol, glycosylated hemoglobin and urinary neopterin were measured by high-performance liquid chromatography. Peripheral blood cell count, D-dimers, fibrinogen, antithrombin, glucose, magnesium, creatinine, uric acid, albumin, C-reactive protein, lipoprotein (a), cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, homocysteine, urinary albumin and N-acetyl-beta-d-glucosaminidase (NAG) were determined with routine methods. No significant differences were observed between patients and 16 controls. Compared to the measurement before the start of therapy, peripheral blood leukocyte and platelet count, hemoglobin, creatinine, HDL cholesterol, retinol, albumin, urinary albumin and NAG decreased, and total cholesterol, LDL cholesterol, triglycerides, neopterin and mean IMT increased significantly after the treatment. Of the 36 patients who had SPECT after treatment, perfusion defects were noted only in two cases, including the patient who had perfusion defects at baseline examination and a patient who did not have a baseline SPECT. In conclusion, a significant increase in carotid IMT, total cholesterol, LDL cholesterol, triglycerides and urinary neopterin and a decrease of peripheral blood leukocyte and platelet counts, hemoglobin, creatinine, HDL cholesterol, retinol, albumin and NAG were observed after the treatment.     

A phase II study of paclitaxel/cisplatin combination in patients with metastatic breast cancer refractory to anthracycline-based chemotherapy

AIMS AND BACKGROUND: To investigate the safety and efficacy of a paclitaxel and cisplatin regimen in a selected group of metastatic breast cancer patients with primary or acquired chemo-resistance to anthracycline-based chemotherapy. PATIENTS AND METHODS: Thirty-eight consecutive women with metastatic breast cancer (PS < or =2) were entered in this phase II trial; all patients had been previously treated for metastatic disease with chemotherapy containing anthracyclines and had shown a progression of the disease during drug administration or after a clinical response lasting less than 6 months. Fifteen patients had received 2 or more chemotherapeutic regimens for advanced disease; 31 patients had > or =2 sites of metastatic disease. Paclitaxel (135 mg/m2) was administered iv by a 3-hr infusion followed by iv infusion of cisplatin (75 mg/m2) on day 1, every 3 weeks for 6 cycles. After the completion of the planned chemotherapy administration, 9 responsive patients continued to receive paclitaxel alone (175 mg/m2) iv, on day 1, every 3 weeks, until disease progression or unacceptable toxicity. RESULTS: A partial clinical response was recorded in 17 cases (45%; 95% CI, 30-64%). The median duration of overall response was 8 months; for the 9 responsive patients who continued treatment with paclitaxel alone, 4 had maintained the partial clinical response at the median follow-up of 24 months from the onset of therapy. The median time to progression was 6 months and median overall survival 8 months. Neurotoxicity was the most frequent adverse effect and caused treatment discontinuation in 5 cases for grade 3-4 paresthesia and/or an arthralgia/myalgia syndrome. Grade 3-4 neutropenia occurred in 16 patients (44%). CONCLUSIONS: Paclitaxel/cisplatin is an active regimen for the treatment of patients with metastatic breast cancer refractory to anthracycline-based chemotherapy. However, the cumulative neurotoxicity should limit the efficacy of prolonged paclitaxel monotherapy in responsive patients.     

Long-term prognostic and predictive factors in 107 stage II/III breast cancer patients treated with anthracycline-based neoadjuvant chemotherapy.

The heterogeneity of therapeutic modalities and eligibility criteria and the lack of long-term follow-up in most reports of neoadjuvant chemotherapy for breast cancer preclude us from drawing conclusions about its value in clinically relevant patient subgroups. The present study aims to identify predictive and prognostic factors in 107 non-inflammatory stage II/III breast cancer patients treated between November 1980 and October 1991 with an anthracycline-based induction regimen before locoregional surgery. Preoperative chemotherapy comprised 3-6 cycles of doxorubicin (pirarubicin after 1986), vindesine, cyclophosphamide and 5-fluorouracil. Type of subsequent surgery and adjuvant treatment were decided individually. In analysis of outcome, univariate comparisons of end points were made using the log-rank test, and significant (P < or = 0.05) pre- and post-therapeutic factors were incorporated in a Cox multivariate analysis. With a median follow-up of 81 months (range 32-164+ months), the median disease-free survival (DFS) is 90.5 months while median overall survival has not yet been reached. Cytoprognostic grade and histopathological response in both the primary and lymph nodes were independent covariates associated with locoregional relapse with or without DFS and overall survival. Eleven patients with pathological complete response remain free of disease with a 68-month median follow-up, while the 18 with residual microscopic disease on the specimen showed a 60% cumulative incidence of locoregional recurrence. Despite encouraging response rates based on clinical or radiological evaluation (87% or 70%), neither method showed any significant correlation with pathological response and failed to contribute prognostic information on patients'' outcome. Pathological evaluation of antitumoral activity of primary chemotherapy remains a major source of prognostic information and might be used to select patients in need of additional adjuvant treatment.     

Response and long-term effect of patients with triple-negative breast cancer receiving neo-adjuvant anthracycline-based chemotherapy

OBJECTIVE The breast cancer lack of expression of estrogen receptor （ER）, progesterone receptor （PR）, and human epidermal growth factor receptor 2 （HER-2） is defined as the Triple-negative breast cancer （TNBC）. Our purpose is to compare the response and long-term effect of the TNBC and non-TNBC patients receiving neo-adjuvant anthracycline-based chemotherapy, and to investigate the mechanisms of TNBC affecting the survivals. METHODS Data of long-term follow-up （median, 5.4 years） of 326 patients who received neo-adjuvant chemotherapy with anthracycline-based regimen, during a period from 2000 to 2003, were analyzed. Expressions of ER, PR, HER-2, P53, Ki-67 and E-cadherin were determined using immunohistochemical staining method. A multivariate Cox regression analysis was used to analyze independent prognostic factors affecting the relapse-free survival （RFS） and overall survival （OS） rates. Clinical effects of the neo-adjuvant anthracycline-based chemotherapeutic regimen and the RFS and OS rates were compared between the patients with TNBC and non-TNBC, and the correlations among the triplenegative phenotype （TNP）, tumor grading and the expressions of P53, Ki-67 and E-cadherins were analyzed. RESULTS TNP, TNM staging, histological grades, clinical response of the neo-adjuvant chemotherapy and pathological complete remission （pCR） rate were the independent prognostic factors affecting the survival rates. Furthermore, 70 （21.5%） of the 326 patients suffered TNBC. Compared with the subjects in non-TNBC group, the patients with TNBC had a significantly higher pCR rate （P = 0.046） and clinical response rate （P = 0.037）, but also decreased 5-year RFS （P = 0.001） and OS （P = 0.004） rates. The RFS and OS rates were not improved in the TNBC patients who achieved a clinical remission after the neo-adjuvant chemotherapy. The triple-negative phenotype was positively correlated with the level of P53, Ki-67 expression （P = 0.007, P = 0.028）, but negatively correlated with level of E-cadherin （P = 0.034）. CONCLUSION Both clinical remission rate and pCR rate of the TNBC patients receiving neo-adjuvant anthracycline-based chemotherapy are high, however, the long-term effect is poor. The mechanism may relate to a strong potential of proliferation and invasive metastasis, as well as lack of an effective therapeutic target in the TNBC patients.     

Mitotic index and benefit of adjuvant anthracycline-based chemotherapy in patients with early breast cancer.

PURPOSE: We have evaluated whether the mitotic index could predict the benefit of adjuvant anthracycline-based chemotherapy in patients with early breast cancer who are eligible for adjuvant chemotherapy according to Saint Gallen guidelines. PATIENTS AND METHODS: A total of 937 patients from a single institution were included in two randomized trials that compared adjuvant anthracycline-based chemotherapy with no chemotherapy. These patients account for 83% of the overall population included in these trials. The first trial included premenopausal patients with node-negative disease, and the second one included postmenopausal patients, regardless of lymph node status. The treatment benefit was assessed according to the number of mitoses per field (x400). RESULTS: The mitotic index was assessable in 888 patients (94%). All the patients presented as either node-positive or an average-risk breast cancer according to 2003 Saint Gallen consensus conference guidelines. The 5-year overall survival rates were 91% and 87% for patients treated or not with adjuvant chemotherapy (P = .09). In patients with low/medium mitotic index (< three mitoses/field; n = 450), the 5-year overall survival rate was 95% for patients treated or not with adjuvant chemotherapy (P = .56). In patients with high mitotic index (>/= three mitoses/field; n = 438), the 5-year overall survival rates were 86% and 79% for patients treated or not treated with adjuvant chemotherapy, respectively (P = .02). CONCLUSION: A high mitotic index is associated with the efficacy of adjuvant anthracycline-based chemotherapy in patients eligible for adjuvant chemotherapy in daily practice.     

Prognostic factors in metastatic breast cancer treated with combination chemotherapy.

Six hundred nineteen patients with metastatic breast cancer, treated with a combination of 5-fluorouracil, Adriamycin, and cyclophosphamide, or close variations of this program, with or without immunotherapy were analyzed retrospectively to identify those host, tumor, or treatment characteristics that might be of prognostic importance in predicting response to chemotherapy and survival from onset of the 5-fluorouracil-Adriamycin-cyclophosphamide treatments. Primary tumor characteristics such as size of primary, number of axillary nodes involved, stage at diagnosis, and type of surgery used for primary treatment were not found to be of prognostic significance. Host characteristics such as age, menstrual status, or family history of breast cancer were similarly unrelated to outcome. Non-Caucasian patients had a lower response rate and somewhat shorter survival than did Caucasians. Pretreatment weight loss, poor performance status, and abnormal biochemical and hematological values were of adverse prognostic significance. An estimate of total extent of disease based on criteria for rating extent of involvement at 12 potential sites was a much more important prognostic factor related to response and survival than actual sites of involvement or the traditional "dominant site" classification. There was a trend, however, for patients with bone involvement to have a longer survival than did patients with metastases to other organ sites. Shorter survival times were observed among patients exposed to extensive prior radiotherapy and those who failed to respond to prior hormonal treatment. The prognostic variables identified in this paper should be used for the design and comparison of clinical trials in the future.     

Dose-dense anthracycline-based chemotherapy for node-positive breast cancer.

PURPOSE: Theoretical considerations and clinical experience suggest that dose-dense chemotherapy may be superior to other approaches using the same drugs. We studied a dose-dense combination of doxorubicin and cyclophosphamide, with or without fluorouracil, as adjuvant therapy. PATIENTS AND METHODS: Patients with resected breast cancer were treated if they were node-positive and estrogen receptor-negative, positive for overexpression of Her-2-neu, or had four or more involved nodes. Doxorubicin was given weekly to a total dose of 480 mg/m(2). Cyclophosphamide 60 mg/m(2) was given daily by mouth during the period of doxorubicin treatment. The first 30 patients received fluorouracil at 300 mg/m(2)/wk intravenously concurrently with doxorubicin administration. In the last 22, it was omitted because of symptomatic hand-foot syndrome in the majority of patients. Filgrastim (granulocyte colony-stimulating factor [G-CSF]) was administered during chemotherapy every day except the day of intravenous administration and continued until 1 week after the completion of the chemotherapy. RESULTS: Between October 20, 1992, and June 10, 1997, we enrolled 52 patients. The mean delivered dose-intensity for doxorubicin was 18.6 mg/m(2)/wk. Hospitalization was required in 6% of patients for reversible febrile neutropenia. There were no acute treatment-related deaths, but one patient subsequently died of acute leukemia with a characteristic translocation for anthracycline-related exposure. At 5 years, the event-free survival was 86% for all patients (95% confidence interval, 75% to 95%). CONCLUSION: Continuous dose-dense chemotherapy with G-CSF support produced encouraging results, which seem to be superior to those expected with "standard" doxorubicin and cyclophosphamide chemotherapy. It deserves a test in the form of a randomized trial where this approach to anthracycline-based treatment is compared with intermittent administration.     

Verbal fluency in breast cancer patients treated with chemotherapy

Background

Cognitive decline caused by chemotherapy used in the treatment of malignant diseases was reported in several studies. ICCTF recommends the diagnosis of cognitive function in patient treated with chemotherapy. One of the suggested method is Verbal Fluency Test (VFT).

Methods

Study was carried out on a group of 30 women with early breast cancer treated with adjuvant chemotherapy and 29 healthy controls. The patients underwent neuropsychological assessment using VFT at three time points: T1: before chemotherapy, T2: mid-chemotherapy and T3: post-chemotherapy. The examination in healthy controls was conducted at the same time intervals.

Results

In phonetic fluency task patients produced more words at T2 compared to T1 (Z = 2.02; p < 0.05) and at T3 compared to T1, both patients (Z = 2.36; p < 0.05) and controls (Z = 2.57; p < 0.01). The patients scored lower than controls (Z = ?2.04; p < 0.05) as well as on average cluster size in the same task (Z = ?2.38; p < 0.05) at T3, while they scored higher on the number of phonetic switches at T2 compared to T1 (Z = 2.62; p < 0.01) and at T3 compared to T1 (Z = 2.50; p < 0.01). In semantic task controls produced more words at T3 than at T1 (Z = 2.62; p < 0.01) and at T3 compared to T2 (Z = 2.89; p < 0.01) and semantic clusters at T3 compared to T2 (Z = 2.43; p < 0.05). In patients, number of clusters was smaller at T3 compared to T2 (Z = ?2.85; p < 0.05), while number of semantic switches was higher at T3 than at T2 (Z = 3.05; p < 0.01). Patients scored also lower than controls on number of semantic switches at T2 (Z = ?2.05; p < 0.05).

Conclusions

Chemotherapy does not decrease verbal fluency, but it has a negative impact on semantic memory.

     

Sexual dysfunction in treated breast cancer patients

Background: This study examined the impact of breast cancer therapyon women's sexuality.Patients and methods: A questionnaire concerning various sexualproblems experienced before and after treatment was anonymously completed by50 women in the outpatient clinic of our hospital's Division of RadiationOncology. To be eligible, subjects had to be disease-free and sexually active.They also had to have undergone surgery at least one year previously and havecompleted CT and/or RT. Fifty-eight percent of the women involved hadundergone mastectomy and 42% had undergone quadrantectomy followed byRT.Results: Ninety percent of the subjects continued sexual activityafter treatment, but there was an increase in the incidence of sexual problemswhich resulted in a slight reduction in the quality of their sex lives.Sixty-four percent of the women experienced an absence of sexual desire and48% low sexual desire, while 38% had dyspareunia, 44%frigidity and 42% lubrication problems. Vaginismus, brief intercourseand female orgasmic disorder were reported by 30% of the subjects.Thirty-six percent suffered from sexual dysfunction before treatment, whichworsened in about 27%, while in 49% of women sexual problemsarose mainly after chemotherapy (26%) or surgery (12%). Aboutone-half experienced changes in the relationship with their partner.Conclusion: Breast cancer patients experienced sexual dysfunction;ours found it easier to discuss the problems with their partner during theirillness (62%) than with doctors and psychologists (15%).     

Bisphosphonates and pathologic complete response to taxane- and anthracycline-based neoadjuvant chemotherapy in patients with breast cancer

BACKGROUND:

Several studies have suggested that bisphosphonates have an antitumor effect. In the current study, the authors sought to evaluate whether the use of bisphosphonates increased the rate of pathological complete response (pCR) in patients with breast cancer.

METHODS:

The authors identified 1449 patients with breast cancer who were receiving taxane‐ and anthracycline‐based neoadjuvant chemotherapy between 1995 and 2007 at The University of Texas MD Anderson Cancer Center. Patients who received bisphosphonates for osteopenia or osteoporosis while receiving chemotherapy were also identified. The primary outcome was the percentage of patients achieving a pCR. Groups were compared using the chi‐square test. A multivariable logistic regression model was fit to examine the relation between the use of bisphosphonates and pCR. An exploratory survival analysis using the Kaplan‐Meier method was performed; groups were compared using the log‐rank test.

RESULTS:

Of the 1449 patients included, 39 (2.7%) received bisphosphonates. Those receiving bisphosphonates were older (P < .001) and less likely to be obese (P = .04). The pCR rate was 25.4% in the bisphosphonate group and 16% in the nonbisphosphonate group (P = .11). In the multivariable model, patients treated with bisphosphonates tended to have higher rates of pCR (odds ratio, 2.18; 95% confidence interval, 0.90‐5.24); however, the difference was not found to be statistically significant. With a median follow‐up of 55 months (range, 3 months‐145 months), no differences in disease recurrence or survival were observed.

CONCLUSIONS:

The use of bisphosphonates at the time of neoadjuvant chemotherapy was not found to be associated with a statistically significant increase in the rates of pCR. The observed estimates suggest a positive effect; however, the small percentage of patients receiving bisphosphonates likely affected the power to detect a statistically significant difference. Cancer 2011;. © 2011 American Cancer Society.     

Survival of patients with metastatic breast cancer treated with either combination or sequential chemotherapy.

One hundred twenty-one patients with metastatic adenocarcinoma of the breast were randomized to concurrent combination therapy or single-drug chemotherapy administered sequentially. Although response frequency and duration of response were significantly increased in patients receiving the combination regimen, survival was not significantly prolonged when compared to those receiving sequential treatment. For the 69 patients free of liver metastasis, median survival was comparable in both treatment arms (14.4 months sequential versus 12.8 months combination). These results indicate that a large subset of patients with metastatic breast cancer may benefit from less aggressive therapeutic regimens. Furthermore, these results illustrate that conclusions of chemotherapy trials in breast cancer based only on response frequency and duration of response represent preliminary results subject to change when final survival information becomes available.     

Risk of pneumonitis in breast cancer patients treated with radiation therapy and combination chemotherapy with paclitaxel.

BACKGROUND: Some chemotherapy (CT) drugs, including taxanes, may enhance the effectiveness of radiation therapy (RT). However, combining these therapies may increase the incidence of radiation pneumonitis, a lung inflammation. In a retrospective cohort study, we evaluated the incidence of radiation pneumonitis in breast cancer patients treated with RT and standard adjuvant CT by use of doxorubicin (Adriamycin) and cyclophosphamide, with and without paclitaxel. METHODS: Forty-one patients with breast cancer were treated with RT and adjuvant CT, including paclitaxel. Paclitaxel and RT (to breast-chest wall in all and lymph nodes in some) were delivered sequentially in 20 patients and concurrently in 21 patients. Paclitaxel was given weekly in some patients and every 3 weeks in other patients. The incidence of radiation pneumonitis was compared with that among patients in our database whose treatments did not include paclitaxel (n = 1286). The percentage of the lung volume irradiated was estimated. The Cox proportional hazards model was used to find covariates that may be associated with the observed outcomes. All P values were two-sided. RESULTS: Radiation pneumonitis developed in six of the 41 patients. Three patients received paclitaxel concurrently with RT, and three received it sequentially (P =.95). The mean percentage of lung volume irradiated was 20% in patients who developed radiation pneumonitis and 22% in those who did not (P =.6). For patients treated with CT including paclitaxel, the crude rate of developing radiation pneumonitis was 14.6% (95% confidence interval [CI] = 5.6% to 29.2%). For patients treated with CT without paclitaxel, the crude rate of pneumonitis was 1.1% (95% CI = 0.2% to 2.3%). The difference between the crude rates with or without paclitaxel is highly statistically significant (P<.0001). The mean time to develop radiation pneumonitis in patients treated concurrently with RT and paclitaxel was statistically significantly shorter in patients receiving paclitaxel weekly than in those receiving it every 3 weeks (P =.002). CONCLUSIONS: The use of paclitaxel and RT in the primary treatment of breast cancer should be undertaken with caution. Clinical trials with the use of combination CT, including paclitaxel plus RT, whether concurrent or sequential, must evaluate carefully the incidence of radiation pneumonitis.     

Prediction of outcome in metastatic breast cancer treated with adriamycin combination chemotherapy

Univariate and multivariate regression methods were used to analyze 17 potential clinical prognostic factors among 138 patients with advanced breast cancer who received Adriamycin-cyclophosphamide combination chemotherapy between 1973 and 1977 at the University of Arizona. Follow-up of patients was through September 1979, and survival data were nearly complete. Different factors varied in the relationship to outcome, but age, treatment, and response were important. Selecting the three most strongly related factors, predictive regression equations were developed, which described three types of possible outcome: 1) objective response (age, treatment, and liver involvement), 2) freedom from relapse (age, lung involvement, and response), and 3) survival (age, the number of involved sites [less than or equal to 2 or > 2], and treatment). Since use of the regression equations is cumbersome for clinical practice, three simplified tables were constructed to readily predict response, duration of response, and survival before the initiation of treatment.