Advanced non-small cell lung cancer in elderly patients: the standard every 3-weekly versus weekly paclitaxel with carboplatin

Paclitaxel and platinum-based chemotherapy is considered to be a standard approach for locally advanced and metastatic non-small cell lung cancer [NSCLC]. In recent years, paclitaxel on a weekly schedule in combination with carboplatin has been widely used because it is associated with a lower incidence of neuropathy and myelosuppression. Otherwise, only a few studies are available in elderly patients with NSCLC. The aim of our study was to evaluate the efficacy and safety of weekly paclitaxel combined with carboplatin compared with the classic 3-weekly schedule of paclitaxel and carboplatin as initial therapy and the feasibility of subsequent maintenance therapy versus observation in elderly patients with locally advanced [stage IIIB] and metastatic [stage IV] NSCLC. Ninty patients >/=65 years with stage IIIB-IV NSCLC were randomly assigned to one of the following arms: arm1, paclitaxel 90 mg/m[2] weekly for 3 of 4 weeks with carboplatin [area under the curve /[AUC/] =6] on day 1 of each 4 week cycle; and arm 2, paclitaxel 200 mg/m[2] with carboplatin [AUC = 6] on day 1 of each 3-week. After four cycles of chemotherapy, those with objective response or stable disease were randomized to weekly paclitaxel [70 mg/ m[2], 3 of 4 weeks] or observation as maintenance therapy. Primary end point was response while second end points included survival and toxicity. Eighty-six patients were evaluable for response, overall responses were recorded in 42.9% in arm 1 versus 31.8% in arm 2; stable disease was 38.1% in arm 1 versus 27.3% in arm 2 and progressive disease was 19% in arm 1 versus 40.9% in arm 2. The median time to progression and median survival times were 7 months and 10.8 months in arm 1 versus 5.6 months and 9 months in arm 2, respectively. The 1-year survival rates were 47.6% in arm 1 versus 36.4% in arm 2. Grade 3/4 anemia was more common in arm 1 [23.8%] than arm 2 [9.1%]. Grade 3/4 neutropenia and febrile neutropenia occurred in 14.3% and 4.7% in arm 1 versus 22.7% and 9.1% in arm 2. Grade 2/3 neuropathy occurred in 4.7% in arm 1 versus 13.6% in arm 2. Efficacy was similar between the weekly regimen and the standard regimen of carboplatin and paclitaxel for elderly patients with advanced NSCLC and may be advantageous based on its favorable tolerability profile

Sequential chemoradiotherapy versus concurrent chemoradiotherapy plus consolidation chemotherapy in unresectable stage III non-small cell lung cancer

To evaluate the efficacy and toxicity of concurrent/consolidation chemoradiotherapy versus sequential chemoradiotherapy in unresectable stage III non-small cell lung cancer [NSCLC]. Between January 2003 and April 2006 thirty-two patients with stage III unresectable NSCLC were randomly assigned to one of the two treatment arms. In the sequential arm, patients received induction chemotherapy with docetaxel [75 mg/m[2]] repeated every 3 weeks for 3 cycles, followed by thoracic radiotherapy at a dose of 61Gy in 33 fractions over 6.5 weeks. In the concurrent/ consolidation arm, the same radiotherapy was started on day 2 with two concurrent cycles of cisplatin 50 mg/m2 on days 1, 8, 29, and 36; etoposide 50 mg/m2 on days 1 through 5 and 29 through 33. Then these patients received consolidation therapy with docetaxel started 4-6 weeks after concurrent chemoradiotherapy, repeated every 3 weeks for 3 cycles at a dose of 75 mg/m[2]. The overall response rate was higher in concurrent/consolidation arm [62.5%] than in sequential arm [43.7%], [P=0.03]. The median survival was 19 months in concurrent/ consolidation arm and 13.6 months in the sequential arm, [P=0.001]. The 2- year survival rate was better in concurrent/ consolidation arm [43.7%] than in the sequential arm [25%], [P=0.03]. Median progression-free survival was longer in concurrent/consolidation arm [11.9 months] than in sequential arm [8 months], [P=0.07]. The major and most frequent toxicity was neutropenia, which was 43.7% in concurrent/consolidation arm versus 56.2% in sequential arm, [P=0.09]. However, esophageal toxicity [>/= grade 3] was relatively higher in concurrent/consolidation arm 18.7% versus 6.2% in sequential arm, [P= 0.05]. Brain metastasis was the most common site of distant failure in both treatment arms. Locoregional failure was more frequent in sequential arm [37.5%] than in concurrent/consolidation arm [18.7%], [P=0.04]. Consolidation docetaxel after concurrent cisplatin/ etoposide with radiotherapy in stage III NSCLC was feasible, tolerable and can be safely administered with relatively low incidence of radiation esophagitis. In addition, treatment outcomes compared favorably with the sequential chemoradiotherapy

Hypofractionated radiotherapy versus conventional fractionated radiotherapy in elderly patients with glioblastoma multiforme

To evaluate efficacy of short-course radiotherapy [RT] in elderly patients [>/= 60 years] with glioblastoma multiforme [GBM], and compare this biological similar short-course radiotherapy with the standard RT. Forty-four elderly patients with GBM were randomly assigned after surgery to receive either a short-course RT [45 Gy in 15 fractions over 3 weeks] or the standard RT [60 Gy in 30 fractions over 6 weeks] to a target volume described as tumor visible on CT scan and a 2-cm margin. The primary end point was overall survival. The overall response rate and median duration of response were 60% and 8.5 months in short-course RT versus 65% and 8 months respectively in standard RT. Improvement in pretreatment performance status and increase in post-treatment corticosteroid dosage were observed in 50% and 25% respectively in short-course RT versus 40% and 50% in standard RT [p=0.09, p=0.031] respectively. Median survival time was 5.9 months in short-course RT versus 5.6 months in standard RT. Six months, one-year survival and progression-free survival rates were 40%, 15% and 30%, 10% respectively in short-course RT versus 45%, 10% and 35%, 5% in standard RT, respectively. In both treatment groups, females did significantly better than males, patients with karnofsky performance status [KPS] 60-70 did significantly better than those with KPS 50, patients having tumors 4-5 cm did significantly better than those with tumors 6-8 cm as well as did those with more radical surgery when compared to those with biopsy only. On multivariate analysis, only tumor size and extent of surgery were found to independently influence survival. Acute toxicity was generally assessed as mild in the two treatment groups. While RT -induced brain necrosis appeared only in one patient received short-course RT, but this patient died from tumor recurrence. Hypofractionated RT is feasible and safe treatment for elderly patients with GBM

Chemotherapy with or without radiotherapy in limited stage aggressive non hodgkin's Lumphoma

To compare the efficacy, toxicity and clinical out come in patients with limited-stage aggressive nondgkin's lymphoma treated with eight cycles of chemotherapy alone or four to six cycles of chemotherapy plus involved field irradiation. One hundred patients with limited aggressive non-Hodgkin's lymphoma were randomly signed to either eight cycles of CHOP alone or four to six cycles of CHOP plus involved-field radiotherapy. The end point were response rate, toxic effects, disease-free survival d overall survival Patients treated with four to six cycles of CHOP is radiotherapy had significantly better disease-free survival in patients treated with CHOP alone. The five-year estimates disease-free survival for patients receiving CHOP plus radiotherapy and for patients receiving CHOP alone were,6% and 65.1%, respectively [p=0.041]. The five-year imates of overall survival for patients receiving CHOP plus radiotherapy and for patients receiving CHOP alone were%and 70%, respectively [p=0.160]. Complete response eswere experienced in 92% in patients treated with CHOP is radiotherapy and 86% in patients treated with CHOP me [p=0.338]. Relapse in original site of disease was significantly higher in patients treated with CHOP alone 9% vs 6.5% in patients treated with CHOP plus radiotherapy =0.007. However, there was no statistically significant difference in systemic relapse between patients treated with CHOP alone [13.9%] and patients treated with CHOP plus radiotherapy [15.2%] [p=0.866]. The adverse effects included a treatment-related deaths in patients treated with eight cycles of CHOP alone versus no treatment-related deaths in ients treated with CHOP plus radiotherapy [p=0.239]. Life threatening toxic effects: grade 3,4 neutropenia were recorded 20% in patients treated with CHOP plus radiotherapy versus% in patients treated with eight cycles of CHOP alone p=0.048, symptoms and signs of congestive heart failure rerecorded in two patients treated with eight cycles of IOP alone, but in no patients treated with CHOP plus iotherapy. For subgroups identified using the Miller modification of the International prognostic Index [IP1], the 5 year disease-free survival and overall survival were signifi-Itly influenced by the number of risk factors in both treat-pt groups [CHOP alone p=0.006, p=0.043 and CHOP plus btherapy p<0.001, p=0.0/3, respectively]. Pour to six cycles of CHOP followed by involved field-radiotherapy are superior to eight cycles of CHOP alone for the treatment of localized aggressive non-Hodgkin's lymphoma. Patients who attained complete response after CHOP plus radiotherapy had more prolonged disease-free survival and higher local control than in patients treated with CHOP alone. IPI risk group was found to be the only significant predictor of overall survival and disease-free survival in both treatment groups.