Stereotactic radiosurgery of residual or recurrent craniopharyngioma, after surgery, with or without radiation therapy

This study evaluated the role of stereotactic radiosurgery in the multimodality management of craniopharyngioma patients whose prior therapies failed. Ten consecutive patients (3 males and 7 females) had radiosurgery for craniopharyngioma during a 10-year interval. Their ages ranged from 9 to 64 years (median, 14.5 years). The median interval between diagnosis and radiosurgery was 46.5 months. In total, 12 stereotactic radiosurgical procedures were performed to control the solid component of the tumor (2 intrasellar and 10 suprasellar tumors). The median tumor volume was 1.35 cm3. One to 9 isocenters with different beam diameters were used; the median marginal dose was 16.4 Gy; and the dose to the optic apparatus was limited to less than 8 Gy. Clinical and imaging follow-up data were obtained at a median of 63 months (range, 13-150 months) from radiosurgery. Overall, 7 of 12 tumors became smaller or vanished within a median of 8.5 months. Prior visual defects objectively improved in 6 patients. One patient with prior visual defect deteriorated further and lost vision 9 months after radiosurgery. Multimodality therapy is often necessary for patients with refractory solid and cystic craniopharyngiomas. Stereotactic radiosurgery is a reasonable option in select patients with small recurrent or residual craniopharyngioma.     

Adjuvant chemotherapy with adriamycin, fluorouracil, cyclophosphamide, methotrexate, with or without tamoxifen in operable breast cancer

Between January 1982 and February 1985, 70 breast cancer patients with histologically confirmed axillary node involvement and T1-3a were treated following surgery with a combination of adriamycin, fluorouracil, cyclophosphamide, methotrexate, with or without tamoxifen according to the estrogen and progesterone receptors state. At 60 months of study (median follow-up, 41 months), the estimated proportion remaining disease-free was 62%. The estimated survival rate was 81%. A comparison of the actuarial disease-free and overall survival with data reported in the literature indicates a similar positive effect of adjuvant systemic therapy as described in adjuvant studies using polychemotherapy regimens. Patient acception of chemotherapy regimen was generally good. This can be accounted for because of an adequate emesis control and real compliance of the patients with the oncologist.     

Adjuvant chemotherapy with fluorouracil, doxorubicin, and cyclophosphamide, with or without Bacillus Calmette-Guerin and with or without irradiation in operable breast cancer. A prospective randomized trial

Between May 1977 and April 1980, 238 patients with operable breast cancer were treated with adjuvant fluorouracil, doxorubicin, and cyclophosphamide (FAC) chemotherapy. All patients were randomized to receive FAC alone or FAC with nonspecific immunotherapy with Bacillus Calmette-Guerin (BCG) vaccine. A randomization for routine postoperative irradiation was included in the study in May 1978. At the median follow-up of 33 months, 53 patients had developed recurrent disease. Up to the present time, there have been no significant differences in the disease-free survival of patients treated with FAC alone from those treated with FAC + BCG (P = 0.21). The disease-free survival for patients treated with and without routine postoperative irradiation was similar (P = 0.99). Disease-free survival of premenopausal and postmenopausal women was similar. The overall estimate of disease-free survival was 72% at 3 years.     

Phase II studies on docetaxel alone every third week,or weekly in combination with gemcitabine in patients with primary locally advanced,metastatic, or recurrent esophageal cancer

Background The purpose of these studies was to compare efficacy and toxicity of docetaxel alone with the combination of gemcitabine and docetaxel for treatment of metastatic esophageal carcinoma. Patients and methods These studies enrolled patients with histopathologically verified squamous cell carcinoma or adenocarcinoma of the esophagus or cardia. Between March 1997 and June 1999, 52 patients were enrolled in the initial Phase II study (Study 1). They were scheduled for treatment with docetaxel 100 mg/m² every third week as a 1-h infusion. The second Phase II study between September 2000 and March 2003 included 65 patients (Study II). They were given docetaxel 30 mg/m², administered as a 30-min i.v. infusion weekly for four times, followed by 2 weeks of rest, and gemcitabine starting with a dose of 750 mg/m² (if well-tolerated 1,000 mg/m²) on days 1 and 15, followed by 3 weeks of rest. A new cycle began on day 36. Patients were premedicated with betamethasone 8 mg p.o. on the evening before, and 8 mg i.v. 30–60 min before the docetaxel infusion. Response was confirmed by computed tomography and assessed at 12 and 24 weeks. Toxicity was assessed according to WHO scales. Results In study I, 38 out of the 52 enrolled patients were valuable. Two patients experienced complete remission (CR) (5%), 10 patients partial remission (PR) (26%), nine patients stable disease (SD) (24%), and 17 patients showed progressive disease (PD) (45%). Toxicity mainly involved leukopenia, which in some cases required hospitalization and treatment with antibiotics. In Study II, 46 out of the 65 enrolled patients (70%) were assessable. Out of these, three patients (7%) had CR, eight patients (17%) had PR, 10 patients (22%) had SD, and 25 (54%) PD. Overall response was 24% while an additional 22% showed stable disease. Toxicity mainly consisted of leucopenia and pain. Conclusion Docetaxel as a single agent is active in esophageal cancer, both in treatment naive and in previously treated patients with recurrent disease. The overall response rate was 31%, with a good-safety profile. The addition of gemcitabine is well tolerated, but adds no efficacy. Weekly administration of docetaxel may be less effective. It demonstrates moderate efficacy and the doses used provide an acceptable safety profile.     

Paclitaxel and carboplatin, alone or with irradiation, in advanced or recurrent endometrial cancer: a phase II study.

PURPOSE: To evaluate the efficacy of carboplatin plus paclitaxel in primarily advanced or recurrent endometrial cancers. PATIENTS AND METHODS: Four distinct patient groups received carboplatin (area under the curve, 5 to 7) plus paclitaxel 175 mg/m(2) for 3 hours at 4-week intervals: group 1 (n = 21), patients with primarily advanced, nonpapillary serous cancers; group 2 (n = 20), the same as group 1 but with papillary serous cancers; group 3 (n = 18), recurrent, nonpapillary serous cancers; and group 4 (n = 4), recurrent, papillary serous cancers. Involved-field irradiation was used in groups 1 and 2 for those with radioencompassable disease. RESULTS: Sixty-three patients were treated. Response rates to chemotherapy in the assessable patients in the four groups were 78% (95% confidence interval [CI], 51% to 100%); 60% (95% CI, 35% to 85%), 56% (95% CI, 34% to 78%), and 50%, respectively. Nineteen patients (90%) in group 1 also were irradiated, and the median failure-free survival time for all 21 patients was 23 months, with a 62% 3-year overall survival rate. Eleven patients (55%) in group 2 were irradiated, and the median failure-free survival time for all 18 patients was 18 months, with a 39% 3-year overall survival rate. The median failure-free interval in the patients in group 3 was 6 months, with a 15-month median overall survival time. Toxicity was manageable, reversible, and predominantly hematologic. Two patients developed neutropenic fever, and three patients, including these two, were hospitalized for complications. CONCLUSION: Carboplatin-paclitaxel is an efficacious, low-toxicity regimen for managing primarily advanced or recurrent endometrial cancers.     

Correction to: Overall survival analysis in patients with metastatic breast cancer and liver or lung metastases treated with eribulin,gemcitabine, or capecitabine

Breast Cancer Research and Treatment - In the original publication, two values provided for landmark survival for patients treated with gemcitabine were incorrectly listed in the text. On page 562,...     

Phase II multi-institutional randomized trial of docetaxel plus cisplatin with or without fluorouracil in patients with untreated, advanced gastric, or gastroesophageal adenocarcinoma.

PURPOSE: The purpose of this study was to define the contribution of docetaxel to combination chemotherapy in the outcome of patients with advanced gastric or gastroesophageal adenocarcinoma. We compared the overall response rate (ORR) and safety of docetaxel plus cisplatin (DC) with DC plus fluorouracil (DCF) to select either DC or DCF as the experimental treatment in the ensuing phase III part of trial V-325. PATIENTS AND METHODS: In this phase II randomized study, untreated patients with confirmed advanced gastric or gastroesophageal adenocarcinoma received either DCF (docetaxel 75 mg/m2, cisplatin 75 mg/m2 on day 1, and fluorouracil 750 mg/m2/d as continuous infusion on days 1 to 5) or DC (docetaxel 85 mg/m2 and cisplatin 75 mg/m2 on day 1) every 3 weeks. An independent data monitoring committee (IDMC) was to select one of the two regimens based primarily on ORR and safety profile. RESULTS: Of 158 randomly assigned patients, 155 (DCF, n = 79; DC, n = 76) received treatment. The confirmed ORR was 43% for DCF (n = 79) and 26% for DC (n = 76). Median time to progression was 5.9 months for DCF and 5.0 months for DC. Median overall survival time was 9.6 months for DCF and 10.5 months for DC. The most frequent grade 3 and 4 events per patient included neutropenia (DCF = 86%; DC = 87%) and GI (DCF = 56%; DC = 30%). CONCLUSION: Both regimens were active, but DCF produced a higher confirmed ORR than DC. Toxicity profiles of DCF were considered manageable. The IDMC chose DCF for the phase III part of V-325, which compares DCF with cisplatin plus fluorouracil.     

Treatment of newly diagnosed AML, RAEB-t or RAEB with lisofylline or placebo in addition to chemotherapy.

To determine whether the addition of lisofylline (LSF) to idarubicin (12 mg/m2 daily x 3) + ara-C (1.5 g/m2 daily x 4) affects the rates of infection, serious infection, CR or mortality during remission induction of newly diagnosed AML, RAEB-t or RAEB, we randomized 70 patients to 3 mg/kg lisofylline or placebo every 6 h i.v., to begin 6 h before the first dose of idarubicin and to continue until recovery of neutrophil and platelet counts or for 28 days, whichever came first. Eligibility required that patients be below age 71 years, have no history of abnormal counts, or chemotherapy for a prior malignancy, and have a creatinine <1.6 mg/dl and bilirubin <3.0 mg/dl. The study was double-blinded and infections were tabulated separately and independently at MD Anderson and by a three-member outside panel of experts. Logistic regression was used to assess the relative effects of treatment arm (LSF or placebo), age, performance status, treatment site (laminar air flow room or not), and cytogenetics on rates of infection and serious infection following the first course of chemotherapy, and on CR rate. There were 84% and 87% concordance between the expert panel and MD Anderson enumerations of infection and serious infections, respectively. Both analyses found no significant (P < 0.05) differences between the rates of infection, or serious infection, in the placebo and LSF groups. CR, 60-day, and overall mortality rates were similar in the two groups, as were time to neutrophil and blood count recovery and outcome once in CR. Logistic regression analyses supported the above conclusions. Severe nausea/vomiting and mucositis were more frequent in the LSF group. Our results suggest that larger studies of LSF in newly diagnosed AML, RAEB-t, or RAEB are not warranted.     

A prospective quality of life study in patients with locally advanced prostate cancer,treated with radiotherapy with or without regional or interstitial hyperthermia

Introduction : The aim of this prospective study was to describe quality of life (QoL) in patients with locally advanced prostate carcinoma treated with conventional radiotherapy and to evaluate the influence of adding regional or interstitial hyperthermia. Materials and methods : All patients were irradiated using a CT-planned conventional three field technique, administering 70 Gy to prostate and vesicles. In two different phase I studies, hyperthermia was added to the radiotherapy. Twelve patients were treated with one interstitial hyperthermia treatment, lasting 60 min. Fourteen patients have been treated with five regional hyperthermia treatments, lasting 75 min each. In both hyperthermia studies, the body, bladder and rectum temperatures remained below safety limits. Patients treated with radiotherapy alone ( n = 58) or combined with regional ( n = 8) or interstitial hyperthermia ( n = 12) completed the European Organization for Research and Treatment of Cancer (EORTC) core questionnaire (C30 + 3), the EORTC prostate cancer module (PR25) and the Rand 36 health survey before treatment and 1 and 6 months after completion of treatment. Analysis of Variance (ANOVA) for repeated measurements has been performed to describe the data. Results : All patient groups were comparable concerning patient characteristics. No significant interaction or difference in QoL has been noticed between the two hyperthermia patient groups and the patient group without hyperthermia. Therefore, all groups were analysed together ( n = 78) to detect QoL changes in time. A deterioration of QoL has been measured from baseline to 1 month after treatment. Fatigue, pain, urinary symptoms, bowel symptoms and financial difficulties increased significantly. Social, physical and role functioning worsened significantly. No differences in QoL were measured 6 months after treatment compared to the baseline measurement, except for a decrease in sexual activity. Conclusions : After radiotherapy with or without hyperthermia only a temporary deterioration of QoL occurs, concerning social, psychological and disease related symptoms. Additional hyperthermia does not seem to decrease QoL.     

Chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone alone or with levamisole or with levamisole plus BCG for malignant lymphoma: a Southwest Oncology Group Study

Between 1977 and 1983 the Southwest Oncology Group (SWOG) evaluated chemotherapy alone (cyclophosphamide, doxorubicin, vincristine, prednisone; CHOP) or chemoimmunotherapy (CHOP-levamisole or CHOP-levamisole-BCG) in a randomized prospective clinical trial involving 715 eligible patients with all types of malignant lymphoma (ML). Of 281 evaluable patients with favorable histologic types of ML, 171 (61%) achieved complete remission (CR) and there was no difference in CR rate, CR duration, or survival according to the type of initial treatment. Of 388 evaluable patients with unfavorable histologic types of ML, 194 (50%) achieved CR. Levamisole appeared to adversely affect CR rates in nodular mixed and nodular large-cell lymphoma and CR duration in patients with unfavorable histology ML. Chemoimmunotherapy with levamisole or levamisole-BCG offers no advantage in terms of CR rates, CR duration, or survival compared to CHOP chemotherapy alone, and levamisole may have had an adverse impact on outcome in certain subtypes of ML.     

Doxorubicin, cyclophosphamide, CCNU, and vincristine with or without cisplatinum in non-small cell lung cancer

To evaluate the role of cisplatinum in the treatment of advanced non-small cell lung cancer, 48 patients received either a doxorubicin (adriamycin) 50 mg/m2 I.V., cyclophosphamide 300 mg/m2 I.V., lomustine (CCNU) 50 mg/m2 p.o., vincristine (oncovin) 1.2 mg/m2 I.V. (ACCO) combination or the same drugs plus cisplatinum 50 mg/m2 I.V. (PACCO) in a prospective sequential trial. No patient had received prior chemotherapy. Patients receiving the two regimens were comparable with regard to median age, performance status, histologic subtype, disease extent, and weight loss. Objective response frequency was only 5% in the initial 20 patients receiving ACCO treatment compared to a response frequency of 28% (7% complete) in the 28 patients receiving cisplatinum in the PACCO treatment arm (p less than 0.06). Patients achieving objective response lived significantly longer than nonresponders (9.1 months vs. 3.8 months, p less than 0.05). Although median survival was similar on the two regimens (6.1 months for ACCO vs. 7.6 months for PACCO), more than four times as many patients were alive after 1 year in the PACCO treatment group (24% vs. 5%). Predominant toxicity consisted of moderately severe nausea and vomiting (63% on PACCO vs. 34% on ACCO, p less than 0.05) and myelosuppression with WBC less than 3,000/mm3 occurring in the majority of patients on both regimens. These results suggest cisplatinum addition to a doxorubicin, cyclophosphamide, lomustine, and vincristine combination may be associated with increased 1-year survival in the non-small cell lung cancer patient population.