Treatment of Malignant Gliomas in the Elderly

The benefit of standard treatment of malignant glioma in older patients is debated. In order to assess the effect of a combination of surgery, radiotherapy and chemotherapy on survival of elderly patients with high grade gliomas, 30 consecutive patients older than 70 years with malignant supratentorial gliomas were studied between 9/93 and 9/96. Median age was 73 years (70–79). The mean Karnofsky performance status (KPS) was 66 (30–100). Patients underwent maximum possible surgery, followed by a course of radiotherapy (45Gy/25 fractions/5 weeks) with 3 or 4 orthogonal beams and a 2cm margin around the tumor bed. The administration of chemotherapy was left at the discretion of the responsible physician and 12 patients received reduced dose nitrosourea-based chemotherapy. The overall median survival was 36 weeks. The median time to progression was 26 weeks. Three months after surgery, 26 patients were alive, 5 were in complete response, 2 in partial response and 10 were stabilized. Pre-radiotherapy KPS was the only significant prognostic factor with a median survival of 40 weeks in patients with KPS 70 and 25 weeks when KPS was >70 (logrank test, p=0.05). In responding and stable patients (57% of the group) the median KPS was 68 and 66 at 1 and 3 months after the completion of radiotherapy. There was no case of radiotherapy-induced dementia with this regimen. Four out of 12 patients who received chemotherapy, experienced WHO grade 3/4 hematotoxicity.This study suggest that some patients older than 70 years with KPS 70 may benefit from the treatment of malignant gliomas with surgery followed by reduced dose of limited field radiotherapy. Further studies are needed to define the most appropriate dose of radiotherapy and to evaluate further the risk/benefit ratio of a reduced dose chemotherapy in this population.     

Vinorelbine as first-line chemotherapy for advanced breast cancer in women 60 years of age or older

Background: Older patients with advanced breast cancer are less likely to receive chemotherapy than younger patients. Vinorelbine is an attractive alternative in this setting because of its clinical activity and low frequency of side effects. This multicenter, phase II trial was designed to assess the safety and efficacy of intravenous vinorelbine as first-line therapy in women 60 years old.Patients and methods: Fifty-six women (median age, 72 years; range 60–84 years), with measurable advanced breast cancer and no prior chemotherapy for metastatic disease, were enrolled and included in the analysis. Vinorelbine 30 mg/m2 was administered weekly for 13 weeks and then every two weeks until development of progressive disease; doses were reduced or delayed to manage toxicity.Results: The objective response rate was 38% (95% confidence interval (95% CI): 24%–51%); median duration of response, nine months; median time to disease progression in all patients, six months. The major dose-limiting toxicity was hematologic, which led to a median dose intensity of 20.6 mg/m2/week. Grade 3–4 nonhematologic toxicity consisted of asthenia (7%); nausea and generalized pain (5%); vomiting, chest pain, abdominal pain, and elevated AST (4%); fever, diarrhea, constipation, and injection site reaction (2%). Neurotoxicity and alopecia were grade 1–2 and relatively infrequent.Conclusions: Vinorelbine offers a promising alternative for the management of advanced breast cancer in elderly patients who are concerned about the subjective side effects of cytotoxic chemotherapy. The dose-limiting toxicity is neutropenia, which is readily managed with dose adjustment. Nonhematologic toxicity, including gastrointestinal side effects, is minimal. Randomized studies are warranted to compare the activity of vinorelbine with that of other regimens in elderly patients.     

Intensity modulated radiotherapy for elderly bladder cancer patients

Background

Radiation therapy plays a central role in the management of many childhood malignancies and Helical Tomotherapy (HT) provides potential to decrease toxicity by limiting the radiation dose to normal structures. The aim of this article was to report preliminary results of our clinical experience with HT in pediatric malignancies.

Methods

In this study 66 consecutive patients younger than 14 years old, treated with HT at our center between January 2006 and April 2010, have been included. We performed statistical analyses to assess the relationship between acute toxicity, graded according to the RTOG criteria, and several clinical and treatment characteristics such as a dose and irradiation volume.

Results

The median age of patients was 5 years. The most common tumor sites were: central nervous system (57%), abdomen (17%) and thorax (6%). The most prevalent histological types were: medulloblastoma (16 patients), neuroblastoma (9 patients) and rhabdomyosarcoma (7 patients). A total of 52 patients were treated for primary disease and 14 patients were treated for recurrent tumors. The majority of the patients (72%) were previously treated with chemotherapy. The median prescribed dose was 51 Gy (range 10-70 Gy). In 81% of cases grade 1 or 2 acute toxicity was observed. There were 11 cases (16,6%) of grade 3 hematological toxicity, two cases of grade 3 skin toxicity and one case of grade 3 emesis. Nine patients (13,6%) had grade 4 hematological toxicity. There were no cases of grade 4 non-hematological toxicities. On the univariate analysis, total dose and craniospinal irradiation (24 cases) were significantly associated with severe toxicity (grade 3 or more), whereas age and chemotherapy were not. On the multivariate analysis, craniospinal irradiation was the only significant independent risk factor for grade 3-4 toxicity.

Conclusion

HT in pediatric population is feasible and safe treatment modality. It is characterized by an acceptable level of acute toxicity that we have seen in this highly selected pediatric patient cohort with clinical features of poor prognosis and/or aggressive therapy needed. Despite of a dosimetrical advantage of HT technique, an exhaustive analysis of long-term follow-up data is needed to assess late toxicity, especially in this potentially sensitive to radiation population.     

Pilot of three objective markers of physical health and chemotherapy toxicity in older adults

BackgroundPatient function is a key part of the clinical decision to offer chemotherapy and has, in earlier studies, been associated with chemotherapy toxicity. Objective testing might be more accurate than patient-reported or physician-assessed physical function, and thus might be a stronger predictor of chemotherapy toxicity in older adults.MethodsPatients, 70 years of age and older, with thoracic or colorectal cancer were recruited. Three physical tests were performed before commencement of a new line of chemotherapy: grip strength, 4-m walk test, and the Timed Up and Go (tug). Our pilot study explored the association between those tests and chemotherapy toxicity.ResultsThe 24 patients recruited had a median age of 74.5 years (range: 70–84 years), and 54.2% had an Eastern Cooperative Oncology Group performance status of 0 or 1. Median score on the Charlson comorbidity index was 1 (range: 0–4). Almost two thirds had metastatic disease, 70% were chemonaïve, and 83.3% were about to receive polychemotherapy. Patients had a mean tug of 13.2 ± 5.7 s and a mean gait speed of 0.74 ± 0.24 m/s; 50% had a grip strength test in the lowest 20th percentile. Grades 3–5 chemotherapy toxicities occurred in 34.7% of the patients; two thirds required a dose reduction or delay; and one third discontinued chemotherapy because of toxicity. Hospitalization attributable to chemotherapy was uncommon (12.5%). A trend toward increased severe chemotherapy toxicity with slower gait speed was observed (p = 0.049).ConclusionsAbnormalities in objective markers of physical function are common in older adults with cancer, even in those deemed fit for chemotherapy. However, those abnormalities were not associated with an increased likelihood of chemotherapy toxicity in the population included in this small pilot study.     

Concurrent chemo-radiotherapy in elderly patients: tolerance and compliance in a series of 137 patients

Introduction

Aggressive cancer treatment is a challenge in elderly patients. The present study aims to assess tolerance in terms of acute toxicity and compliance of concurrent chemo-radiotherapy (cCRT) in a series of patients aged ≥70 years.

Materials and methods

Clinical records of patients aged ≥70 years who underwent cCRT between January 2005 and December 2013 were reviewed. Concurrent CRT had curative intent in 134 patients (97.8 %) and palliative intent in 3 patients (2.2 %). Chemotherapy (CT) drugs and schedule were selected according to tumor histology. Radiotherapy median dose was 45.0 Gy (range 11–70 Gy) for curative purposes and 54 Gy (range 40–56 Gy) for palliative purposes. Incidence of acute toxicity and compliance to cCRT were analyzed and correlated with age, Karnofsky Performance Status (KPS), and Charlson Comorbidity Index (CCI).

Results

Overall, 137 patients, 82 males (60 %) and 55 females (40 %), median age 74 years (range 70–90 years) were analyzed. Concurrent CRT schedule was completed by 132 patients (96.4 %). Thirty-one of these patients (23.5 %) temporarily interrupted treatment. Hematological toxicity with grade ≥1 was observed in 25 patients (18.2 %), gastrointestinal toxicity in 55 (40.1 %), and genitourinary in 13 (9.5 %). Mucositis with grade ≥1 was recorded in 19 patients (13.9 %). No statistical significant correlation between KPS, CCI, and toxicity was found. A correlation trend between mucositis and patient age (p = 0.05) was observed.

Conclusion

Concurrent CRT for elderly was feasible and quite well tolerated. Great attention in prescribing CT dose should be paid to limit acute toxicity.

     

Relation between age and clearance rate of nine investigational anticancer drugs from phase I pharmacokinetic data

Aging influences the disposition and effects of several classes of drugs. Although drug clearance rate is correlated with toxicity for many anticancer drugs, few data have been published concerning the relationship of aging and clearance of chemotherapy. This study was performed to identify any relationship between age and clearance rate for anticancer drugs in phase I trials at the Johns Hopkins Oncology Center. In a retrospective study, we examined the clinical and pharmacokinetic data for 344 adults (aged 21–77 years) who received 9 phase I drugs with linear clearance in 13 clinical trials. We sought correlations between age and clearance for each drug and for the whole group. Data available for 9 of the 13 trials were used to compare age (<65 or >65 years) versus dose delivered [< the maximum tolerated dose (MTD) vs the MTD] or toxicity (< grade 3 vs grade 3). Of 344 patients, 81 (23.5%) were >65 years old, 34 (9.9%) were 70 years old, and 5 (1.5%) were 75 years old. There was no significant correlation between drug clearance and age for individual drugs or the group as a whole. There was no significant difference between patients of the older and younger age groups with regard to dose or toxicity. Although only a small number of patients aged 75 years were treated, our results suggest that the elderly do not experience greater toxicity even when treated at doses comparable with those given younger patients and should not be excluded from phase I trials on the basis of age. As the population of the United States ages, more elderly patients will be candidates for chemotherapy. A more thorough examination of the relationships between age, clearance rate, and toxicity can be accomplished as active drugs enter phase II/III studies.Supported in part by Public Health Service grants N01CM07302 and RR00035-33 from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services, and by a grant from the American Federation for Aging Research/Hartford Foundation     

Advanced colorectal cancer in the elderly: results of consecutive trials with 5-fluorouracil-based chemotherapy

To evaluate toxicity and efficacy of chemotherapy in elderly patients (≥65 years of age) with advanced colorectal cancer, data from two consecutive trials conducted between 1984 and 1995 at the National Institute for Cancer Research were analysed comparing the results of treatment in those 65 years of age or older and in those younger than 65 years. Of 215 patients recruited, 82 elderly patients (median age 70 years, median performance status 1) received one of the following regimens based on 5-fluorouracil (5-FU): (1) weekly 5-FU 600 mg/m² i.v. bolus (30 patients); (2) weekly 5-FU 600 mg/m² bolus plus leucovorin (LV) 500 mg/m² 2-h i.v. infusion (28 patients); (3) Weekly 5-FU 2600 mg/m² 24-h continuous i.v. infusion plus LV 100 mg 4-h i.v. infusion and 50 mg orally every 4 h for five doses (24 patients). Overall, 1071 chemotherapy cycles were administered with a median number of 12 courses per patient. The main side effects were diarrhoea, observed in 38% of patients, stomatitis in 24% of patients and hand-foot syndrome in 13% of patients, and haematological toxicity affected only 15% of patients. No patient suffered grade IV toxicity. In three patients chemotherapy was discontinued because of toxicity (two patients suffered grade III diarrhoea, one patient grade III hand-foot syndrome). No significant difference in toxicity was evident between patients older than or younger than 65 years. Analysis of median dose intensity demonstrated no difference between the two groups. Overall objective response was observed in 18% (95% confidence limits 11–29) of elderly patients (15/82) in comparison with 23% (95% CL 17–32) of patients <65 years of age (31/133 pts). In conclusion, chemotherapy in elderly patients with advanced colorectal cancer is a safe and effective treatment with acceptable toxicity and comparable objective response rates. Received: 6 January 1998 / Accepted: 27 February 1998     

Neoadjuvant hyperfractionated-accelerated radiotherapy with concomitant chemotherapy in esophageal cancer: phase II study

Purpose

Concomitant use of chemotherapy and a radiation dose schedule that is more efficient compared to conventional radiotherapy may provide better outcomes in patients with esophageal cancer. This study aimed to assess the efficacy and tolerability of neoadjuvant cisplatin-based chemotherapy and hyperfractionated accelerated radiotherapy regimen in this group of patients.

Methods and materials

A total of 20 newly diagnosed treatment-naïve esophageal cancer patients were included in the study. Neoadjuvant cisplatin and 5-FU were given with 28-day intervals in a total of three courses. Along with the third course of chemotherapy, hyperfractionated accelerated radiotherapy (HART) was given with the following dose schedule: 5760 cGy/36 fr/16 day.

Results

All patients could receive the planned RT dose of 5760 cGy. Odynophagia was the most frequent grade III acute toxicity (50%). None of the acute toxicity reactions required treatment discontinuation. Grade III or higher subacute/late toxicity occurred in 10 patients (75%) including 5 deaths, mostly esophageal. Radiologically, 8 patients (40%) had complete response, 8 (40%) had partial response, and 3 (15%) had stable disease, with only 1 patient (5%) having progressive disease. Seven patients underwent surgery. Overall, 8 patients (40%) had local control. The 5 years overall survival rate was 38.1%.

Conclusions

Neoadjuvant hyperfractionated accelerated radiotherapy plus chemotherapy may help to target local disease control and increase survival in patients with esophageal cancer. Further studies to improve neoadjuvant and radical chemoradiotherapy dose schedules are warranted for maximum tumor control rates with minimal toxicity.Key Words: Neoadjuvant radiochemotherapy, esophageal cancer, hyperfractionated-accelerated radiotherapy, toxicity, safety     

Weekly docetaxel as salvage therapy in patients with gemcitabine-refractory metastatic pancreatic cancer

Gemcitabine-based chemotherapy provides very limited disease control in the treatment of advanced pancreatic cancer. Approximately half of the patients failing upfront treatment present good performance status and are willing to undergo further treatment. Docetaxel activity against pancreatic cancer is reported both in the preclinical and clinical setting. Between November 2004 and November 2005, 10 patients (median age 59; median KPS 80) with metastatic pancreatic adenocarcinoma, progressive disease after gemcitabine-containing chemotherapy, KPS >50, adequate organ function, were treated with weekly docetaxel at 30 mg/m-(2) until progressive disease. Docetaxel dose intensity was 100% of the intended dose. No grade >2 toxicity was observed. No objective response to treatment was obtained. Median progression-free survival was 1.5 months (range 1-3.5 months); median survival was 4.0 months (range 2.0-7.5). Weekly administration of single-agent docetaxel does not seem to have any activity in the treatment of gemcitabine-resistant metastatic pancreatic cancer.     

Efficacy and safety of combination chemotherapy with mitomycin and vinorelbine for the treatment of advanced non-small cell lung cancer

BACKGROUND: Aim of this study was to evaluate efficacy, toxicity and tolerability of chemotherapy with a combination of mitomycin and vinorelbine (M/V) in patients with advanced non-small cell lung cancer (NSCLC). METHODS: We enrolled 110 patients (median age 67 years) with locally advanced or metastatic NSCLC, who had no prior chemotherapy or progressive disease after at least one prior chemotherapy regimen. 45 patients (41%) were > or =70 years old. All patients received vinorelbine 25mg/m(2) (d1,8) and mitomycin 8mg/m(2) (d1) every 3-4 weeks. Restaging was performed by CT-scan after every two courses M/V according to RECIST criteria. RESULTS: M/V was well tolerated, even in patients with a poor performance status or > or =70 years Median progression free survival was 4.4 months. Median overall survival was 9.0 months with a 1-year survival rate of 39%. Partial response was observed in 15% and stable disease in 51% of patients. Both hematological and non-hematological toxicities were generally mild. CTC grade 3 toxicities observed included neutropenia in 3%, anemia in 3%, thrombocytopenia in 1% and suspected pneumonitis in 2% of patients. Except neutropenia in 2% and acute dyspnea in 1%, there were no other grade 4 toxicities and no treatment associated casualties. There was no relevant difference in outcome or toxicity between patients > or =70 and <70 years. CONCLUSIONS: M/V seems to be a well-tolerated and effective chemotherapy regimen with low toxicity in patients with advanced NSCLC. It seems to be an interesting option even for patients > or =70 years or with a reduced performance status.     

Weekly administration of topotecan–paclitaxel as second-line treatment in ovarian cancer

Purpose To investigate the weekly administration of topotecan combined with paclitaxel in pretreated advanced ovarian cancer patients; our objectives were to determine efficacy, toxicity and survival Methods The chemotherapy agents, topotecan and paclitaxel were administered on a weekly basis for 3 consecutive weeks, every 28 days. The plan was to give three courses (each course included three once-weekly infusions). The dose of topotecan was 1.75 mg/m² and of paclitaxel 70 mg/m². Results From January 2004 until January 2006, 45 patients were enrolled in this multicenter trial; 44 patients were evaluable for response and toxicity. The median age was 60 years old (range 39–82 years) and performance status was 0–2. Thirty-nine patients were in stage III and 5 in stage IV. All patients had been pretreated with carboplatin or cisplatin in combination with paclitaxel. Complete and partial responses were seen in 39% of the patients, stable disease in 43% and progressive disease in 18%; median survival time was 9 months, range 2–24+ months, (95% CI: 7.9–10.2). There was a notable absence of grade 3 toxicity except for neutropenia in 11% of the patients. Conclusion The combination of topotecan and paclitaxel administered on a weekly basis is a well-tolerated chemotherapy schedule. The response rate of 39% is quite high for patients with pretreated ovarian cancer.     

Advanced or metastatic gastric cancer in elderly patients: clinicopathological, prognostic factors and treatments

Purpose

To analyze the clinicopathological features, prognostic factors, treatment efficacy and safety among elderly patients with advanced or metastatic gastric cancer.

Methods

Three hundred and nineteen patients aged 65 years and older, diagnosed with advanced or metastatic gastric cancer, were followed and data were retrospectively collected, reviewed and analyzed.

Results

The elderly patients carried specific clinicopathological characteristics. Body mass index (BMI), number of metastatic lesions, ascites, Karnofsky performance score (KPS), tumor differentiation grade, lactate dehydrogenase (LDH) level, local treatment, and chemotherapy were the independent prognostic factors. Serum LDH level was superior to the serum CEA level in the prognosis of advanced or metastatic gastric cancer in older patients. Cisplatin-based regimen, chemotherapy cycles, metastatic lesions, LDH level, and supraclavicular lymph node metastasis were the independent prognostic factors in 220 patients receiving chemotherapy. The toxicity was mild and tolerable.

Conclusion

KPS, BMI and a well-differentiated histopathology were factors favoring longer survival, whereas elevated serum LDH and a greater number of metastatic lesions were associated with poor prognosis among those elderly patients. Cisplatin-based chemotherapy provided survival benefits and mild toxicity.     

Multicenter safety study of mFOLFOX6 for unresectable advanced/recurrent colorectal cancer in elderly patients

Background

Combination chemotherapy with oxaliplatin plus 5-fluorouracil/leucovorin (FOLFOX) has become a standard regimen for colorectal cancer. An increase of adverse events with combination chemotherapy is predicted in elderly patients, and it remains controversial whether they should receive the same chemotherapy as younger patients. Accordingly, this study of modified FOLFOX6 (mFOLFOX6) therapy was performed to compare its safety between elderly and non-elderly patients.

Methods

We prospectively studies 14 non-elderly patients aged <70 years old and 8 elderly patients aged ≥ 70 years with unresectable advanced/recurrent colorectal cancer who received mFOLFOX6 therapy during the period from March 2006 to March 2007. Adverse events and the response to treatment were compared between the elderly and non-elderly groups.

Results

The main adverse events were neutropenia and peripheral neuropathy, which occurred in 62.5% (≥ grade 3) and 87.5% (≥ grade 1) of elderly patients. The grade and frequency of adverse events were similar in the elderly and non-elderly groups. In some patients with neutropenia, treatment could be continued without reducing the dose of oxaliplatin by deleting bolus 5-fluorouracil. A correlation was found between the cumulative dose of oxaliplatin and the severity of neuropathy, and there were 2 elderly and 3 younger patients in whom discontinuation of treatment was necessary due to peripheral neuropathy. The median number of treatment cycles was 10.0 and 9.5 in the non-elderly and elderly groups, respectively. The response rate was 60.0% in the non-elderly and 50.0% in the elderly group, while the disease control rate was 100% and 83.3% respectively, showing no age-related difference.

Conclusion

mFOLFOX6 therapy was well-tolerated and effective in both non-elderly and elderly patients. However, discontinuation of treatment was sometimes necessary due to peripheral neuropathy, which is dose-limiting toxicity of this therapy.     

Long-term follow-up in managing anaplastic astrocytoma by multimodality approach with surgery followed by postoperative radiotherapy and PCV-chemotherapy: phase II trial

Overall survival and progression-free survival after 5 and 10 years of 31 patients with malignant glioma treated by a combination of surgery, postoperative radiotherapy, and chemotherapy with a PCV regimen (procarbazine, CCNU [lomustine] and vincristine) is described. Parameters were evaluated by age at diagnosis, gender, ethnic origin, pre- and postsurgery Karnofsky Performance Status (KPS) score, limit and amount of surgical resection, histopathologic type, number of chemotherapy courses, time between surgery and radiotherapy, response to combined therapy, and dosage and type of radiotherapy. Progression-free survival was 29% at 24 months and 22% at 60 and 120 months. Overall survival was 47%, 36%, and 36% after 24, 60, and 120 months, respectively. Favorable prognostic factors for survival in univariate analysis were pre- and postoperative KPS (> or =70; p = 0.015; p = 0.0025, respectively), age of patients (<40; p = 0.01), number of chemotherapy cycles (> or =6; p = 0.02), and radiation dose (> or =60 Gy; p = 0.0015). The only significant prognostic factors for overall survival in a stepwise multivariate analysis were irradiation dose (p = 0.0001), number of chemotherapy cycles (p = 0.001), and preoperative KPS (p = 0.05); for progression-free survival it was number of chemotherapy cycles (p = 0.004). Survival was not affected by excision size, radiation method, histopathologic type of tumor, gender, ethnic origin, or time lapsed between surgery and irradiation.     

影响肺癌化疗患者发生肺部感染的危险因素分析

目的探讨影响肺癌化疗患者发生肺部感染的危险因素。方法对296例肺癌化疗患者进行回归性分析,收集临床资料,统计肺部感染发生率,应用单因素检验及logistic回归模型筛选出影响肺部感染的危险因素。结果296例患者中54例发生肺部感染,感染率为18. 24%。单因素分析显示,肺癌化疗患者肺部感染发生与年龄、吸烟史、高血压、糖尿病、TNM分期、治疗方法、化疗用药方案、化疗周期、化疗前KPS评分、白蛋白含量有关(P <0. 05)。多因素Logisitic回归分析显示,年龄≥60岁、TNM分期为Ⅲ~Ⅳ期、化疗用药≥2种、化疗周期> 4个、化疗前KPS评分<80分、白蛋白水平均为肺癌化疗患者肺部感染发生的危险因素(P <0. 05)。结论肺癌化疗患者肺部感染发生率较高,危险因素众多,应积极采取针对措施加强控制。     

Efficacy of uracil/tegafur (UFT) plus oral Leucovorin (LV) therapy for colorectal cancer in elderly patients

BACKGROUND & AIMS: The uracil/tegafur (UFT) plus oral Leucovorin (LV) regimen is one of the standard chemotherapy modalities for colorectal cancer, and has been reported to have fewer side effects. In this study, we investigated the efficacy and toxicity of UFT/LV regimen in elderly patients. PATIENTS AND METHODS: The subjects were twelve patients older than 70 years (median age, 76 years), who received a UFT/LV regimen for colorectal cancer between January 2004 and June 2005. Chemotherapy was attempted for metastatic colorectal cancer in seven patients and for postoperative adjuvant chemotherapy in five patients. The response rate and toxicity were compared with those of patients younger than 70 years old. RESULTS: Four courses of chemotherapy, in median, were delivered. The regimen consisting of UFT 300 mg/m(2) was completed in all patients. One patient achieved a complete response and another patient a partial response, thus resulting in an overall response rate of 28.6%. Three patients experienced Grade 1 diarrhea, and seven patients had Grade 1 or 2 anemia. Grade 3 or 4 toxicity was not recognized in all patients. CONCLUSIONS: Treatment with UFT/LV regimen is effective and well tolerated in elderly as well as younger patients.     

Safety profile and activity of lower capecitabine dose in patients with metastatic breast cancer

PURPOSE: Capecitabine is an orally administered precursor of 5'-deoxy-5-fluorouridine that was rationally designed to generate 5-fluorouracil (5-FU) preferentially in tumor tissue. The drug enables chronic dosing that mimics continuous infusion of 5-FU. Phase II trials of capecitabine at 1250 mg/m2 twice daily for 14 days followed by 7 days of rest, is active in anthracycline- and taxane-pretreated patients; the main toxicity is palmar-plantar erythrodysesthesia, diarrhea, and nausea. To overcome these side effects, the dose has been reduced to 1000 mg/m2 twice daily with a better therapeutic profile and encouraging efficacy. The aim of our study was to confirm safety and activity of capecitabine at lower doses in patients with metastatic breast cancer (MBC). PATIENTS AND METHODS: Thirty-seven patients with advanced breast cancer entered the study. The first 7 patients were treated with capecitabine 1250 mg/m2 twice daily (for 14 days followed by 7 days of rest) and the next 30 patients with capecitabine 1000 mg/m2. The median age was 62 years (range, 38-87 years). Thirteen patients were chemotherapy naive and 24 were pretreated with chemotherapy (9 patients, 1 line; 15 patients, > or = 2 lines). Anthracyclines and/or taxane schedules were administered in 22 patients. Soft tissue metastases were documented in 36 patients; visceral metastases in 24 patients; visceral and soft tissue metastases in 23 patients. RESULTS: Thirty patients were evaluable for response (5 at "higher" dose and 25 at "lower" dose) and all for toxicity. Overall objective response rate was 57% (5 complete responses and 12 partial responses); 95% CI, 39%-74%; stable disease 20% and progressive disease 23%. Eight of 13 chemotherapy-naive patients (61.5%) and 9 of 24 pretreated patients (37.5%) responded to capecitabine, according to the intent-to-treat principle (6 of 9 responses were obtained at a lower dose). Three responses at the "higher" dose and 14 at the "lower" dose were reported. Median time to progression was 7 months (range, 1-38 months) and median overall survival was 19 months (range, 2-47 months). Toxicity was as follows: grade 2/3 palmar-plantar erythrodysesthesia in 9 patients (24%), grade 2/3 asthenia in 7 patients (19%), grade 2 vomiting in 4 patients (11%), grade 2 renal toxicity in 1 patient, grade 2 skin reaction in 1 patient, and suspected cardiac toxicity in 1 patient. CONCLUSION: Our study confirmed that a lower dose of capecitabine has a good toxicity profile and is active in patients with MBC.     

探讨接受BSA指导用药剂量的乳腺癌化疗患者个体间多西他赛药代动力学差异

目的:探索乳腺癌患者接受体表面积（BSA）指导用药剂量的多西他赛(DTX)化疗后患者体内药代动力学多态性,以揭示患者体内药物暴露的差异。方法:采用纳米增强免疫比浊法测定258例患者血浆中的DTX浓度,计算每位患者的关键药代动力学参数AUC,并进行DTX药物浓度监测。结果:258例患者个体间的AUC值分布在0.40~2.67 mg·h/L,变异系数40.6%。采用不同化疗方案的各组患者的AUC并未显示出显著的差异,<50岁以及50~70岁组患者的AUC显著低于>70岁组患者的AUC(P=0.007,P=0.012)。结论:采用BSA指导用药剂量的DTX化疗可导致个体患者间的疗效和毒副作用出现巨大差异,需优化现有的用药剂量制定方案以提高乳腺癌患者尤其是老年乳腺癌患者（>70岁）DTX药物有效性并降低毒副作用。     

Chemotherapy Toxicity in Older Adults Optimized by Geriatric Assessment and Intervention: A Non-Comparative Analysis

The Comprehensive Geriatric Assessment (CGA) is recommended to guide treatment choices in older patients with cancer. Patients ≥ 70 years referred to our oncology service with a new cancer diagnosis are screened using the G-8. Patients with a score of ≤14 are eligible to attend the Geriatric Oncology and Liaison (GOAL) Clinic in our institution, with referral based on physician discretion. Referred patients undergo multidimensional assessments at baseline. CGA domains assessed include mobility, nutritional, cognitive, and psychological status. Chemotherapy toxicity risk is estimated using the Cancer Aging and Research Group (CARG) calculator. We undertook a retrospective analysis of patients attending the GOAL clinic over a 30-month period to April 2021. The objective was to determine rates of treatment dose modifications, delays, discontinuation, and unscheduled hospitalizations as surrogates for cytotoxic therapy toxicity in these patients. These data were collected retrospectively. Ninety-four patients received chemotherapy; the median age was 76 (70–87) and 45 were female (48%). Seventy-five (80%) had an ECOG PS of 0–1. Seventy-two (77%) had gastrointestinal cancer, and most had stage III (47%) or IV (40%) disease. Chemotherapy with curative intent was received by 51% (n = 48) and 51% received monotherapy. From the CGA, the median Timed Up and Go was 11 s (7.79–31.6), and 90% reported no falls in the prior 6 months. The median BMI was 26.93 (15.43–39.25), with 70% at risk or frankly malnourished by the Mini Nutritional Assessment. Twenty-seven (29%) patients had impaired cognitive function. Forty-three (46%) had a high risk of toxicity based on the baseline CARG toxicity calculator. Twenty-six (28%) required dose reduction, 55% (n = 52) required a dose delay, and 36% (n = 34) had a hospitalization due to toxicity. Thirty-nine patients (42%) discontinued treatment due to toxicity. Despite intensive assessment, clinical optimization and personalized treatment decisions, older adults with cancer remain at high risk of chemotherapy toxicity.     

Treatment of Supratentorial Glioblastoma Multiforme with Radiotherapy and a Combination of BCNU and Tamoxifen: A Phase II Study

From May 1990 to November 1994, 70 consecutive patients suffering from glioblastoma multiforme were treated following surgery with conventional radiotherapy and adjuvant IV BCNU administered alone or in combination with tamoxifen. Twenty-five patients received BCNU alone (control group A) while 24 patients also received 40mg of tamoxifen (TMX) PO daily (group B) and 21 received 100mg of TMX PO daily (group C). There were no significant differences between the 3 groups concerning age, type of resection and median post-operative Karnofsky performance status (KPS). Blood toxicity over grade II occurred in 33.5% of patients receiving TMX versus 12% of patients treated with BCNU alone (p<0.05).Deep venous thrombosis complications were observed in 4 patients of each TMX group, whereas they were not observed in the control group (p<0.04). Median time to tumor progression (MTTP) was 35 weeks in the control group and 27 weeks in both TMX groups B and C. Median survival time (MST) was 56, 66 and 51 weeks, respectively.These results suggest that the addition of TMX to standard treatment of glioblastomas does not affect the time to tumor progression and overall survival but may increase the risk of deep venous thrombosis or nitrosourea-induced blood toxicity.