Gemcitabine, cisplatin and dexamethasone in patients with recurrent or refractory B-cell lymphoma not candidates for high-dose therapy

High dose therapy [HDT] with autologous stem-cell transplantation is the treatment of choice for patients with relapsed lymphoma, but is not appropriate for all patients. Effective and less toxic alternatives to conventional salvage regimens are needed. To determine efficacy and safety of gemcitabine, cisplatin and dexamethasone in patients with relapsed or refractory B-cell lymphoma who are not candidates for high dose therapy. Thirty patients with relapsed or refractory B-cell lymphoma were treated with gemcitabine 1000mg/m[2] intravenously [iv] on days 1 and 8, cisplatin 75mg/m[2] iv on day 1, and dexamethasone 40mg/m[2] orally on days 1-4, every 21 days on an outpatient, for a maximum of 6 cycles. The majority [66.7%] had diffuse large B-cell lymphoma. All 30 patients were evaluable for response and toxicity, Five patients [16.7%] achieved complete remission and 12 patients [40%] had partial remission of their disease with an overall response rate of 56.7%. The 2-year progression-free and overall survival rates were 20% and 33.3% respectively. Myelosuppression was the main toxicity. Grade 3 and 4 neutropenia occurred in 40% and 26.7% respectively. Grade 3 and 4 thrombocytopenia occurred in 30% and 23.3% respectively. Only one patient had neutropenic sepsis. Grade 3 non hematological toxicity was minimal with no patients suffered from grade 4 toxicity. Gemcitabine in combination with cisplatin and dexamethasone is an effective and well tolerated salvage regimen in patients with relapsed or refractory B-cell lymphoma who are not eligible for HDT

Concurrent chemoradiotherapy plus consolidation chemotherapy compared with concurrent chemoradiotherapy alone in unresectable stage III non-mall-cell lung cancer

To evaluate the addition of consolidation chemotherapy to concurrent Chemoradiotherapy in patients with locally advanced unresectable stage III non-small-cell lung cancer as regard efficacy and safety. Forty one patients were randomly assigned to either concomitant Chemoradiotherapy alone [arm 1, n = 19] or concomitant Chemoradiotherapy followed by consolidation chemotherapy [arm 2, n = 22]. In the concurrent arm, patients received weekly paclitaxel [45 mg/m[2]], carboplatin [100 mg/m[2]] and concomitant thoracic radiotherapy at a dose of 63 Gy in 34 fractions over 7 weeks. In the concurrent/consolidation arm, the same regimen was administered followed by two additional courses of paclitaxel [200 mg/m[2]] and carboplatin [300 mg/m[2]] every 3 weeks. Pre-treatment characteristics were well balanced between the two arms. Median survival was 13 months in the concurrent arm and 16.5 months in the concurrent/consolidation arm [p = 0.59]. One-, 2-, and 3- year survival rates were better in the concurrent/consolidation arm [63.6%, 36.4%, and 13.6% respectively] than in the concurrent arm [52.6%, 26.3%, and 10.5% respectively], p = 0.48. Grade 3/4 granulocytopenia occurred in 16% and 27% of patients on the concurrent and concurrent/consolidation arms respectively [p = 0.38]. The most common grade 3/4 non-hematological toxicity was esophagitis. It was more frequent in the consolidation arm than in the concurrent arm [32% v 21%], p = 0.43. Concurrent Chemoradiotherapy followed by consolidation chemotherapy represent the preferred regimen for the treatment of unresected stage III NSCLC. However, toxicity, particularly, non-hematological toxicity, remains a major obstacle

Concomitant boost radiotherapy plus concurrent cisplatin for muscle invasive bladder cancer

To determine the efficacy and toxicity of accelerated concomitant boost radiotherapy [RT] plus concurrent cisplatin in patients with muscle invasive bladder cancer. Sixty four patients with muscle invading transitional cell bladder cancer were entered into a protocol of transurethral resection of the bladder tumor [TURBT] followed by concurrent cisplatin [10mg/m[2] thrice weekly] and accelerated concomitant boost radiotherapy. The whole pelvis was treated by l.8Gy conventional daily fractions up to a total dose of 45Gy. A concomitant boost limited to the bladder was delivered as a second daily fraction [1.4Gy] during the last 3 weeks up to a total dose of 66Gy. The patients were evaluated for local control, toxicity and survival. All but two patients completed the radiotherapy protocol. Fifty eight patients received the full doses of cisplatin. Grade 3 acute urinary toxicity was observed in 10 patients [15.6%]. Also, 6 patients [9.4%] presented with acute grade 3 bowel toxicity. Eight patients [12.6%] experienced late grade 3 toxicity [4 with bladder and 4 with bowel toxicity]. The 3-year actuarial local control, distant disease control and overall survival rates were 60% [95% CI, 50.1-69.3], 65.6% [95% CI, 53.7%-74.3%], and 37.5% [95% CI, 26.1%-45.9%] respectively. The results of our protocol of acclerated concomitant boost radiotherapy with concurrent cisplatin, as regard locoregional control and overall survival, did not appear to be improved in comparison with other studies combining cisplatin and standard conventional fractionation, moreover the observed toxicity was higher

Hypofractionated radiotherapy for elderly or younger low-performance status glioblastoma patients: a prospective randomized clinical trial

To prospectively compare standard conventionally fractionated radiation therapy [RT] with hypofractionated radiotherapy in elderly or younger, low-performance status, glioblastoma patients. Thirty eight patients with glioblastoma multiform [GBM] who are elderly [>/= 60 years] or younger, with low performance status [ECOG >2] were randomly assigned after surgery to standard adjuvant radiotherapy [60Gy in 30 fractions over 6 weeks] or short course regimen [50Gy in 20 fractions over 4 weeks]. The primary end point of the study was overall survival [OS]. Secondary end points were progression-free survival [PFS], the proportion of patients alive at 6 and 12 months, acute treatment toxicity and quality of life [QOL]. The median survivals were similar for the two groups: 6.5 months for the 6-week group and 6 months for the 4-week group [HR, 1.16 and 95% CI, 0.59 to 1.86 and p=0.71]. The survival probabilities at 6 and 12 months were also similar, 55.6% and 27.8% versus 52.9% and 23.5% for the 6-week and 4-week treatment arms respectively [p=0.86 and 0.74 respectively]. The median times to tumor progression were similar for the two groups: 3.5 months for standard RT versus 3 months for the shorter course treatment [HR, 1.15 and 95% CI, 0.59 to 1.89 and p=0.83]. The 6-months PFS rates were 38.9% and 35.3% for the 6-week and 4-week arms respectively [p=0.80]. The median KPS were similar at the times of assessment for the two groups. It was 65, 60 and 70, 60 at first and second follow-up for the 6-week and 4-week groups respectively [p=0.79 and 0.68 respectively]. Thirty three percent of patients in the conventionally fractionated arm required an increase in steroid therapy versus 35.3% in the hypofractionated arm [p=0.62]. There is no significant differences in survival, progression-free survival, acute toxicity, or quality of life between standard radiotherapy or hypofractionated radiotherapy. In view of the 2-week reduction in overall treatment time, we regard the shorter course of radiotherapy as a reasonable treatment option for elderly or younger low performance status glioblastoma patients

Capecitabine plus vinorelbine combination therapy in patients with metastatic breast cancer pretreated with anthracyclines and/or taxanes

To determine efficacy and safety of capecitabine plus vinorelbine in metastatic breast cancer [MBC] patients who relapse after adjuvant and/or first line chemotherapy [including anthracyclines and/or taxanes]. From April 2007 to March 2003, 26 eligible patients were recruited. Patients were treated by Vinorelbine in a dose of 25 mg/m[2] administered on days 1 and 8 every 3 weeks with Capecitabine orally twice daily [1000 mg/m[2]] for 14 consecutive days starting on day 1 of the cycle. The median age was 56 years [range 31-67]; ECOG PS 0-1, [9-12]; ER/PR +ve [19]; prior chemotherapy anthracvcyclines/taxanes [26/8]. After chemotherapy the overall response rates were 48% [1 CR and 11PR] [95% confidence interval [CI], 35.9-59.7]. In additional seven patients [28%] showed disease stabilization. The median time to disease progression was seven months and median overall survival was 17.5 months. Myelosuppression was the predominant toxicity. Toxicities included grades III and IV neutropenia in 7 [2 7%] and 3 [11.5%] patients respectively, and only one patient developed febrile neutropenia. Grade III hand-foot syndrome occurred only in One patient. Other nonhematologic toxicities were minimal and manageable. This study demonstrated that capecitabine plus vinorelbine combination was effective and well tolerated in MBC patients even after failure of anthracycline-and/or taxane-containing regimens

Weekly irinotecan in patients with progressive or rapidly recurrent colorectal cancer pretreated with fluorouracil-based chemotherapy

To prospectively evaluate efficacy and tolerability of weekly irinotecan [CPT-11] in patients with advanced colorectal carcinoma [CRC] that had recurred or progressed following fluorouracil [5-FU]-based therapy. Forty eight patients were enrolled in this study. They were treated with irrinotecan 125 mg/m[2] intravenously [IV] every week for 4 weeks, followed by a 2- week rest. All patients were accessible for toxicity and only 44 patients completed one full course of therapy and were accessable for response. Nine patients [20.5%] attained partial response [95% CI, 10% to 27%] and no cases achieved complete response. The median duration of response was 7 months [range4to 11.5 months]. The median survival time was 10 months [95% CI 8.2 to 13.1 months] and the 1-year survival rate was 43.8% [95% CI, 33% to 53%]. Median time to progression was 4.0 months [95% CI, 2.6 to 5.1 months]. Grade 3-4 diarrhea was observed in 17 patients [35.4%], grade 3-4 nausea and vomiting in 3 patients [6.3%] and 4 patients [8.3%] respectively. Grade 3-4 neutropenia was reported in 5 patients [31.3%]. Grade 3-4 febrile neutropenia or infection affected only 2 patients [4.2%]. Weekly schedule of irinotecan has demon strated significant activity against colorectal cancer that has progressed during or shortly after treatment with 5-FU-based chemotherapy. Diarrhea is the most frequent dose limiting toxicity but can be substantially reduced through appropriate interventional management

Paclitaxel plus carboplatin versus carboplatin alone in women with platinum-sensitive recurrent ovarian carcinoma

To compare the efficacy and safety of paclitaxel plus carboplatin versus carboplatin alone in the treatment of patients with platinum-sensitive recurrent ovarian carcinoma. Forty patients with platinum-sensitive ovarian carcinoma relapsing after 6 months of being treatment-free and with no more than two previous chemo-therapy lines were enrolled in this trial. Twenty one patients were randomized to receive carboplatin [300 mg/m[2] and 19 to receive the same dose of carboplatin plus paclitaxel [175mg/m[2] The primary outcome measure was objective response. Secondary outcomes were progression-free survival [PFS], overall survival [OS] and toxicity. The response rate in the combination arm was 79% [26% complete response [CR] and 53% partial response [PR]] compared with 48% in the carboplatin arm [19% CR and 29 PRI [p=0.041]. Median PFS was higher in paclitaxel carboplatin arm [12 versus 8 months]. Median OS was also better in the combination arm [24 versus 18 months]. However, these differences were not statistically significant [p=0.23 and 0.35 respectively]. No significant differences were observed in grade 3-4 hematological toxicity. Conversely, alopecia, mucositis, myalgia/arthralgia and sensory neuropathy were more frequent in the combination arm and the differences were statistically significant [p=0.0009, 0.027, 0.001, and 0.027 respectively]. Paclitaxel plus carboplatin is a tolerable regimen. It seems to be more effective among patients with platinum-sensitive recurrent ovarian carcinoma compared with single-agent carboplatin

Radiation with concurrent late chemotherapy [chemoboost] for locally advanced squamous cell carcinomas of the head and neck

The aim of this study was to determine efficacy and toxicity of a treatment regimen that combined conventionally fractionated radiation therapy [70Gy over 7 weeks] with chemotherapy [cisplatin and fluorouracil], given concurrently in the last two weeks of treatment, in patients with locally advanced squamous cell carcinoma of the head and neck. Thirty patients with biopsy-proven squamous cell carcinoma of the head and neck were enrolled in this study. They received a course of radiotherapy [7OGy over 7 weeks] concurrent with 360mg/m[2] of 5-fluorouracil and 10mg/m[2] of cisplatin given daily with each radiation dose during the last two weeks. Nineteen patients had a complete response to chemoradiation, giving a complete response rate of 63.3%. Eleven patients had persistent disease [partial response was achieved in 8 patients [26.7%], stable disease in 2 patients [6.7%] and progressive disease in 1 patient [1.33%]]. Local control was good among the 19 patients who obtained a complete response, 15 remained free of local recurrent disease, 4 have relapsed. Locoregional relapse-free survival was 79% [15/19] at 2 years. However, considering the 11 patients with persistent disease, there was 15 patients [50%] failed at 2 years and locoregional failure-free survival was 50% [15/30]. Of the 30 patients entered the study, 4 patients developed distant metastases as first relapse and 2 as subsequent failure. Therefore, an estimated 20% of the patients [6/30] developed distant metastases by 2 years either as first or subsequent failure, and distant metastases failure-free survival was 80% [24/30] at 2 years. No patients developed locoregional relapse or distant metastases during the third year. The estimated overall survival was 53.3% at 2 years and 46.7% at 3 years. Grade 3 mucositis was observed in 73.3% of patients. Acute skin reaction was severe and protracted, grade 3 developed in 50% of the patients, and the median duration of skin reaction was 5 weeks. Grade 3 and 4 neutropenia was observed in 16.6% of the patients, febrile neuropenia in 6.7% and grade 3 thrombocytopenia in 3.3%. The chemoboost regimen is feasible and active approach for combining chemotherapy and radiation in the management of locally advanced head and neck cancer. It is associated with significant but acceptable toxicity profile

Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin and cisplatin in locally advanced or metastatic bladder cancer

This trial was undertaken to compare gemcitabine plus cisplatin [GC] versus methotrexate, vinblastine, doxoruhicin and cisplatin [MVAC] in patients with locally advanced or metastatic transitional cell carcinoma [TCC] of the bladder. A total of 46 patients with locally advanced [n=21] or metastatic [n=25] TCC of the bladder and with no prior systemic chemotherapy were included in this study. They were randomized to GC [gemcitabine 1000 mg/m2 days 1, 8 and 15, cisplatin 70 mg/m2 day 2] or standard MVAC [methotrexate 30 mg/m2 on days 2, 15, 22, doxorubicin 30 mg/m2 on day 2 and cisplatin 70 mg/m2 on day 2]. The cycles were repeated every 28 days for a maximum of six cycles. It was found that gemcitabine/cisplatin combination is an active and safe treatment option in advanced and metastatic bladder cancer. It is a real alternative to MVAC with the same clinical benefits and significantly improving safety and tolerability

Activity and safety of navelbine and fractionated dose doxorubicin as first line therapy for advanced breast cancer

Very promising results have been obtained by vinorelbine-doxorubicin combination in the treatment of advanced breast cancer. However previous experience with schedules in which the doxorubicin dose was administered on day 1 alone were associated with a high level of cardiac toxicity. There is evidence that fractionating the dose of doxorubicin and administering it at weekly intervals may reduce the cardiac toxicity without substantially impairing the efficacy. To asses the efficacy and tolerability of vinorelbine and fractionated dose doxorubicin [the total dose was divided into two administrations on days 1 and 8] in patients with advanced breast cancer. Fifty-two patients with locally advanced or metastatic breast cancer who had received no prior chemotherapy except in an adjuvant setting were entered into the study. They were treated vinorelbine 25 mg/m[2] plus doxorubicin 25 mg/m[2] both administered in day 1 and 8 every three weeks. Objective responses were observed in 30 patients [71, 4%]. There were 7 [16.6%] complete responses [CR] and 23 [54.8%] partial responses [PR]. In addition 10 patients [23.8%] had stable disease [SD] and 2 [4.8%] progressed while on treatment. Twenty of 28 patients with visceral disease responded to treatment [71.4%]. The median duration of response was 11.5 months [range, 2 to > 24+] and the median overall survival was 21.5 months [range 2 to > 36+]. Hematological toxicity was predominantly related to neutropenia with Grade 3-4 reported in 18.1% of the cycles. Alopecia was reported in 66.7% of the patients. Grade 3 nausea/vomiting in 3.6% of the cycles. No clinically significant cases of cardiac dysfunction were seen. The fractionated schedule of vinorelbine and doxorubicin is associated with excellent tolerability [especially cardiac], coupled with high levels of activity comparable to those observed using the un-fractionated regimen