Oral vinorelbine plus cisplatin followed by maintenance oral vinorelbine as first-line treatment for advanced non-small cell lung cancer.

PURPOSE: Vinorelbine plus cisplatin is a commonly used doublet for the treatment of advanced non-small cell lung cancer (NSCLC). This study aimed to investigate the efficacy of oral vinorelbine as maintenance therapy in advanced NSCLC. METHODS: This multicenter phase II open-label, non-comparative study was designed to evaluate the three-weekly combination of cisplatin 80 mg/m(2) on day 1 in combination with oral vinorelbine on day 1 and 8 in advanced NSCLC. RESULTS: Thirty-nine patients were enrolled; median age was 63 years (range 42-82). In the response-evaluable population (n = 38), objective response after induction therapy was observed in 18 (47 %) patients with two (5 %) patients achieving complete response. Stable disease was observed in nine (24 %) patients. The median duration of response was 6 months. Eighteen (46 %) patients received oral vinorelbine as maintenance therapy. The median PFS for the whole population and for the maintenance therapy group was 4.9 [95 % CI (2.8-6.9)] and 6.7 [95 % CI (3.7-9.7)] months, respectively, while the overall survival was 8.7 [95 % CI (5.4-11.9)] and 11 [95 % CI (8.3-13.7)] months, respectively. The main observed overall hematologic toxicities were grade 3 anemia (8 %) and grade 3/4 neutropenia (8 %). CONCLUSION: Maintenance therapy with single-agent oral vinorelbine is feasible and well tolerated; it seems to extend the efficacy of the combination regimen with the advantage of being convenient to patients.

Sequential therapy with gemcitabine and Carboplatin followed by Paclitaxel as first line treatment for advanced urothelial cancer.

OBJECTIVE: Gemcitabine and platinum-based compounds represent the new standard combination therapy for bladder cancer. In this study, we evaluate the efficacy and safety of gemcitabine and carboplatin followed sequentially by paclitaxel in 27 patients with advanced transitional cell carcinoma. METHODS: This phase II multicentre study was based on the doublet gemcitabine 800 mg/m2 and carboplatin area under the concentration-time curve 2 on days 1 and 8 every 21 days for 4 cycles, followed sequentially by paclitaxel 60 mg/m(2)/w for 12 consecutive weeks. The disease was assessed after each sequence. RESULTS: Primary tumor was localized in the bladder and renal pelvis in 25 and 2 patients, respectively. Twenty patients completed all 4 cycles of the gemcitabine and carboplatin sequence. Mean number of cycles was 3.5 (range 1 to 4). Toxicities were mainly hematologic, including Grade 3 neutropenia and anemia in 3 patients. OBJECTIVE response was noted in 11 pts (40.7%), including 1 complete response (CR) and 10 partial responses (PR). Three patients had stable disease and 11 progressed. Among the 20 patients, 14 received the second sequence. Mean number of paclitaxel injections was 7 (range 2 to 12). Toxicities were limited to diarrhea and neurotoxicity in 1 patient each. OBJECTIVE response was documented in 6 patients (30%) (3 CR and 3 PR), including the improvement of PR into CR in 2 patients. Median duration of response was 6 months. After a median follow-up of 7 months, 21 patients died and 6 remained alive, including 2 who maintained CR and 1 PR.Sixteen patients had locally advanced disease and 11 had metastatic disease, better prognostic was noticed with patients with locally advanced disease. CONCLUSION: the sequential approach of treatment for advanced urothelial cancer using gemcitabine and carboplatine followed by paclitaxel seems to be a safer alternative to the combined triplet, but due to the limited number of patients this study failed to improve outcome. Further investigations with larger population are required.

Adjuvant chemo-radiation for gastric adenocarcinoma: an institutional experience.

BACKGROUND: Studies have shown that surgery alone is less than satisfactory in the management of early gastric cancer, with cure rates approaching 40%. The role of adjuvant therapy was indefinite until three large, randomized controlled trials showed the survival benefit of adjuvant therapy over surgery alone. Chemoradiation therapy has been criticized for its high toxicity. METHODS: 24 patients diagnosed between September 2001 and July 2007 were treated with adjuvant chemoradiation. 18 patients had the classical MacDonald regimen of 4500 cGy of XRT and chemotherapy with 5-fluorouracil (5FU) and leucovorin, while chemotherapy consisted of 5FU/Cisplatin for 6 patients. RESULTS: This series consisted of non-metastatic patients, 17 females and 7 males with a median age of 62.5 years. 23 patients (96%) had a performance status of 0 or 1. The full course of radiation therapy (4500 cGy) was completed by 22 patients (91.7%). Only 7 patients (36.8%) completed the total planned courses of chemotherapy. 2 local relapses (10%), 2 regional relapses (10%) and 2 distant relapses (10%) were recorded. Time to progression has not been reached. 9 patients (37.5%) died during follow-up with a median overall survival of 75 months. Patients lost a mean of 4 Kgs during radiation therapy. We recorded 6 episodes of febrile neutropenia and the most frequent toxicity was gastro-intestinal in 17 patients (70.8%) with 9 (36%) patients suffering grade 3 or 4 toxicity and 5 patients (20%) suffering from grade 3 or 4 neutropenia. 4 (17%) patients required total parenteral nutrition for a mean duration of 20 days. 4 patients suffered septic shock (17%) and 1 patient developed a deep venous thrombosis and a pulmonary embolus. CONCLUSIONS: Adjuvant chemo-radiation for gastric cancer is a standard at our institution and has resulted in few relapses and an interesting median survival. Toxicity rates were serious and this remains a harsh regimen with only 36.8% of patients completing the full planned courses of chemotherapy. This is due to hematological toxicity, mainly febrile neutropenia. This should prompt us to review the subsequent chemotherapy protocol and make it more tolerable.

Role of capecitabine and irinotecan combination therapy in advanced or metastatic gastric cancer.

Gastric cancer is one of the most common cancers and the second leading cause of cancer-related death. So far, the only curative treatment for gastric cancer is surgery. However, approximately half of all patients present with nonoperable tumors. Therefore, combination chemotherapy regimens are being accepted nowadays as first-line treatment for this disease. Despite the numerous efforts of randomized trials on advanced gastric cancer, no globally accepted regimen has yet been established. Historically, the most widely adopted protocols use 5-fluorouracil or platinum-based therapy with a response rate not exceeding 50% in combination therapy with a high rate of toxicity. Recently, many new drugs have emerged on the market and have been used in treating advanced or metastatic gastric cancer allowing the creation of new combination regimens with better clinical benefit. The combination of irinotecan plus capecitabine is one of these new combinations that seem to provide an acceptable response rate and good toxicity profile. In this article, we review the efficacy, tolerability, and feasibility of this combination for the treatment of advanced or metastatic gastric cancer and we summarize the clinical trials using this regimen.

Role of low dose capecitabine combined to irinotecan in advanced and metastatic gastric cancer.

Chemotherapy has a proven role in advanced and metastatic gastric cancer (AMGC) significantly improving quality of life and prolonging survival compared with best supportive care alone. Multiple regimens have been explored. The choice of treatment should be individualized and tailored to the patient's overall conditions and preference. This manuscript is divided into two sections. The first section illustrates the results of a phase II trial combining weekly irinotecan and low dose capecitabine in the management of untreated AMGC patients. The second section aims to identify the current optimal place of this combination in the management of AMGC in the light of the latest advances. In this manuscript we detail our phase II trial which showed objective response rate of 47% (15 patients), disease stabilization of 28% (9 patients), and overall tumor control rate of 75% (24 patients). Median time to progression and overall survival were 5.8 and 8 months, respectively. Grades III-IV toxicities were reported in 7 cases. Low-dose capecitabine plus irinotecan is effective in the treatment of AMGC with an acceptable toxicity profile. Compared to the recent published data, this combination is indicated in the second-line treatment of AMGC and in the first-line treatment where a contraindication for docetaxel- and/or oxaliplatin-based regimen is present.

Weekly docetaxel, zoledronic acid and estramustine in hormone-refractory prostate cancer (HRPC).

Treatment options for patients with hormone refractory prostate cancer (HRPC) showed unsatisfactory outcomes. Docetaxel-based combinations could offer more promising and tolerated results. A phase II trial was conducted with the combination of zoledronic acid, docetaxel and estramustine. Eligibility consisted of metastatic prostate adenocarcinoma with objective progression or rising prostate specific antigen levels (PSA) despite androgen deprivation therapy. Zoledronic acid was given at a dose of 4 mg on day 1, docetaxel (25 mg/m2) on days 1, 8 and 15, and estramustine orally at 140 mg two times daily on days 1 to 21 of a 28-day cycle. Twenty-seven patients were enrolled between October 2002 and November 2004. Median age was 68 years (53-83 years). A total of 124 cycles were administered with a median of 4.6 cycles per patient (1-8 cycles). The major toxicities were grades 1 to 3 anemia (55%), fatigue (15%), alopecia (11%) and hypocalcemia (11%). Two patients presented with deep venous thrombosis and died from pulmonary embolism. Another third patient died from Stevens-Johnson syndrome and grade 4 hepatic toxicity. Out of the 25 patients assessed for efficacy, 13 (52%) had a biologic response (>50% PSA decline). Three (21%) patients among the 14 with measurable disease had objective response: 1 complete response (CR) and 2 partial responses (PR). Response duration was 2 months for PR and 4 months for CR. A total of 12 patients (48%) experienced clinical benefit with pain reduction. This combination seemed effective; however toxic deaths especially from venous thrombosis counterbalanced the advantage of this regimen.

Gemcitabine plus carboplatin combination therapy as second-line treatment in patients with relapsed breast cancer.

This study was designed to determine the safety and efficacy of the combination therapy of gemcitabine plus carboplatin when used as a second-line treatment in patients with metastatic breast cancer (MBC). From February 2002 to May 2003, 30 previously treated patients with adenocarcinoma of the breast received gemcitabine 1000 mg/m2 on days 1 and 8 plus carboplatin to an area under the curve (AUC) of 5 on day 1. The carboplatin dose was changed to an AUC of 4.5 because of toxicity, with cycles repeated every 3 weeks. Among 30 patients enrolled, 25 were assessable for response rate (RR). There was no complete response; 9 patients (30%) had partial response, for an overall RR of 30%. The median time to progression for the study group was 20.47 weeks (range, 8-46 weeks). Treatment-related toxicities included grade 3/4 neutropenia in 50% of patients (20% of whom had febrile neutropenia), grade 3/4 anemia in 26.6% of patients, and grade 3/4 thrombocytopenia in 30%. Eleven patients (36.67%) had grade 1 alopecia, and 1 patient (3.33%) had grade 2 alopecia. Moderate nausea was observed in 8 patients (26.67%), and vomiting occurred in 7 patients. Four patients had asthenia and 3 (10%) experienced stomatitis. Three patients discontinued treatment because of hematologic toxicity (thrombocytopenia) and 2 patients are still receiving treatment. Carboplatin plus gemcitabine is an active combination for patients with MBC despite significant but manageable hematologic toxicity.

Granulocytic sarcoma with spinal cord compression in chronic myelogenous leukemia: a case report.

We report on a 19-year-old man with a spinal cord compression secondary to granulocytic sarcoma (GS) as the initial presentation of a chronic myelogenous leukemia (CML). Blastic crisis developed two months later. According to our case report and to the literature, the diagnosis of GS could predict a rapid progression to blastic phase.