Capecitabine as salvage treatment in relapsed nasopharyngeal carcinoma: a phase II study.

PURPOSE: To evaluate the efficacy of capecitabine (Xeloda) as rescue treatment (2nd, 3rd and 4th line) in patients with relapsed nasopharyngeal carcinoma (NPC) in a phase II study. PATIENTS AND METHODS: Between 5/2002-11/2005, 23 relapsed NPC patients (17 locoregional relapse, 3 metastatic, 3 locoregional + metastatic) received capecitabine 2500 mg/m(2)/d, days 1-14 every 3 weeks, until progression or for a maximum of 6 cycles. PATIENT CHARACTERISTICS: 23 patients (14 men, 9 women) with median age 46 years (range 15-59); ECOG performance status 1 n=21, 2 n=2; histology: undifferentiated carcinoma (WHO type III) n=21, non-keratinizing epidermoid carcinoma (WHO type II), n=2. Capecitabine was given as 2nd--(13 patients), 3rd--(7 patients), and 4th--(3 patients) line chemotherapy. Previous chemotherapy regimes were epirubicin + cisplatin, paclitaxel + carboplatin, paclitaxel + 5-fluorouracil and leucovorin (5-FU/LV) or methotrexate. 104 cycles were given (median 5, range 2-6). Two (9%) patients achieved complete response (CR); 9 (39%) partial response (PR); 9 (39%) stable disease (SD) and 3 (13%) progressed (PD). Toxicity was mild without toxic deaths or grade 4 toxicities. The most frequent toxicities (grades 1-3) were anemia (38%), hand-foot syndrome (23%), leukopenia (13%) and diarrhea (7%). Median follow-up was 10 months (range 2-44). Median overall survival was not reached at 18 months and actuarial one-year survival was 62% (95% confidence interval/CI: 41-80). Median progression-free survival was 14 months. CONCLUSION: Capecitabine is active in relapsed NPC patients, achieving 48% objective responses, with mild toxicity. It is an attractive therapy to be administered in an outpatient setting.

Quality of life and treatment related toxicity in 335 patients with locally advanced cervical carcinoma treated by two chemoradiation regimens.

PURPOSE: Concomitant chemoradiotherapy (CT/RT) is the gold standard for advanced cervical carcinoma, but with frequent debates over treatment schedules and toxicity. This study compared 2 concomitant CT/RT regimens in terms of quality of life (QoL) and acute toxicity. PATIENTS AND METHODS: Between March 2003 and March 2005, 335 patients with stage IIB-IIIB cervical carcinoma were evaluated in a randomized single-center phase III trial at the Oncology Institute Cluj-Napoca. Patients received concurrent CT/RT with cisplatin 20 mg/m(2), days 1-5, every 21 days (arm A, n=171) or 40 mg/m(2)/weekly (arm B, n=164). QoL was estimated using the EORTC QLQ-30, v.3.0 questionnaire and acute toxicity using the common toxicity criteria (CTC) v.2.0. RESULTS: Significant improvement of global health status (p <0.01) and a decrease in pain (p <0.01) was observed in arm A. In arm B fatigue increased (p=0.01) and role functioning diminished (p=0.05). In both arms depression, nausea, vomiting and diarrhea increased (p <0.05). Gastrointestinal toxicity was similar in both arms (76% vs. 77.5%). Hemoglobin drop was higher in arm B: 75% vs. 63% (p=0.02), while no differences were seen in leukocyte and platelet toxicity. CONCLUSION: Concomitant CT/RT with cisplatin 20 mg/m(2) x 5 days every 21 days has better impact on patients' QoL and lower toxicity compared with the weekly chemotherapy regimen.

Clinical results of medium dose rate brachytherapy combined with external beam radiotherapy in the treatment of advanced cervical carcinoma.

PURPOSE: To evaluate the overall and disease-free survival of patients with advanced cervical carcinoma (FIGO stages IIB-IIIB) treated with external beam radiotherapy (EBRT) and medium dose rate brachytherapy (MDR-BT) plus/minus surgery. PATIENTS AND METHODS: One hundred and seven patients received preoperative RT (group A) and 154 were treated with definitive RT (group B); 73 patients in both groups also received cisplatin as radiosensitizer. EBRT delivered as preoperative reached a total dose of 44-46 Gy/pelvis, whereas the definitive RT reached a total dose of 62-64 Gy with standard fractionation. MDR-BT was performed with a LDR/MDR Cs-137 Selectron machine; 10 Gy/point A were delivered in the preoperative group A and 14 Gy/point A/, 1-2 fractions in group B. Cisplatin as radiosensitizer was administered during EBRT at a dose of 20 mg/m(2)/day for 5 days with 21 days interval between cycles. RESULTS: With a median follow-up of 44.4 months (range 3.4-61.6) the overall survival at 3 years in group A was 92% vs. 68% for group B (p<0.01). According to FIGO stages 3-year overall survival was 88% in stage IIB, 79% in IIIA and 60% in IIIB (p<0.01). Three-year local control was 73.5% (192 patients). Thirty-three (13%) patients developed locoregional recurrences, and another 8 (3.07%) locoregional recurrences plus distant metastases. CONCLUSION: The association of EBRT with MDR-BT represents an effective treatment in advanced cervical carcinoma. A significant difference in 3-year overall survival was found, favoring preoperative RT, with a very good rate of local control.

Concurrent chemoradiotherapy with vinorelbine and a platinum compound followed by consolidation chemotherapy for unresectable stage III non-small cell lung cancer: preliminary results of a phase II study.

PURPOSE: To determine the efficacy, toxicity and survival of concurrent therapy with vinorelbine and a platinum compound with radiotherapy (RT), followed by consolidation chemotherapy with the same drugs, for locally advanced non small cell lung cancer (NSCLC). PATIENTS AND METHODS: Fifty-seven patients with stage III NSCLC were included in this phase II study: median age 56 years (range 44-71), males / females 49/8, ECOG performance status (PS) 1/2=27/30, stage IIIA/ IIIB 11/46, squamous cell carcinoma 44, adenocarcinoma 7, adenoid cystic carcinoma 1 and large cell carcinoma 5. Treatment consisted of 2 cycles of chemotherapy with vinorelbine and cisplatin or carboplatin, given concurrently with RT, followed by 2-4 more cycles of consolidation chemotherapy with the same drugs. Twenty-two patients received amifostine for radio- and chemoprotection. RESULTS: Grade 3 or 4 toxicities were neutropenia and esophagitis in 19% of the patients each, and gastrointestinal toxicity in 17% of the patients. Of the 55 patients evaluable for response, 23.64% achieved complete response (CR) and 40% partial response (PR) (overall response rate 63.64%). Progression-free survival curves showed 1- and 2-year values of 42% and 21%, respectively, and median time to progression 10.5 months. The 1- and 2- year disease-specific survival was 58% and 29%, and the median overall survival 15 months. CONCLUSION: Preliminary analysis indicates that concurrent vinorelbine and a platinum compound with RT followed by consolidation chemotherapy with the same drugs for advanced stage III NSCLC is well tolerated, has considerable activity and positive impact on survival.

Paclitaxel and carboplatin in relapsed or metastatic nasopharyngeal carcinoma: a multicenter phase II study.

PURPOSE: This multicenter phase II study was conducted to investigate the activity and toxicity of a combination of paclitaxel and carboplatin delivered on an outpatient basis in relapsed/ metastatic nasopharyngeal carcinoma patients. PATIENTS AND METHODS: Patients aged>/= 18 years with histologically proven recurrent or metastatic nasopharyngeal carcinoma, an Eastern Cooperative Oncology Group (ECOG) performance status /= 12 weeks were eligible. Measurable disease outside prior radiotherapy ports was required, unless a subsequent progression of the lesion was documented. An interval of >/= 12 months was required between the previous chemotherapy (neoadjuvant, concurrent chemoradiotherapy or adjuvant) and study entry. Prior radiotherapy or surgery were allowed. All patients had adequate bone marrow (WBC >4000/mL, platelets >100000/mL), hepatic (bilirubin <1,5 mg/dL, SGPT <1.5xN), and renal function (serum creatinine <1.5 mg/dL or creatinine clearance >60 mL/min). Chemotherapy consisted of paclitaxel 175 mg/m(2), given as a 3-hour infusion, followed by carboplatin dosed to an area under the concentration- time curve (AUC) of 6 mg*min/mL, administered every 21 days. RESULTS: 40 patients entered the study. There were 3 complete responders (CR) and 8 partial responders (PR), for an overall response rate (ORR) of 27.5% (95% confidence interval - C.I.: 14.5-44). Median time to progression (TTP) was 3.5 months, and median survival was 11.5 months. Grade 3-4 toxicity included leucopenia (17.5% of the patients), anaemia (17.5%), thrombocytopenia (10%), neutropenia (7.5%), and peripheral neuropathy (2.5%). CONCLUSION: These data indicate that the combination of paclitaxel and carboplatin can be safely administered on an outpatient basis, but it is only moderately active against relapsed/metastatic nasopharyngeal carcinoma patients.

First-line chemotherapy with topotecan and etoposide in advanced small cell lung cancer. A phase II study.

PURPOSE: Topotecan has recently shown activity in small cell lung cancer (SCLC) patients. The aim of the present phase II study was to assess the antitumor activity and toxicity of the combination of topotecan plus etoposide in chemotherapynaive patients with advanced SCLC on an outpatient basis. PATIENTS AND METHODS: From December 1998 to February 2001 24 previously untreated patients with histologically proven advanced (stage IIIB and IV) SCLC received topotecan 1.2 mg/m(2), days 1-5, followed by etoposide 100 mg/m(2), days 8-10, every 3 weeks, up to 6 cycles (less if progressive disease). RESULTS: Twenty-two patients were males and 2 females. Their median age was 54 years (range 37-67 years). World Health Organization (WHO) performance status (PS) was 0-1 in 12 patients and 2 in 12. AJCC stage IIIB was found in 6 patients and IV in 18. TOXICITY: 76 cycles (median 3.5 cycles) were given with no toxic deaths. Grade 4 toxicity was registered in 10 (13%) cycles for neutropenia, 4 (5%) cycles for anaemia, 1 (1.3%) cycle for thrombocytopenia and 1 (1.3%) cycle for diarrhea. Activity: among 23 evaluable patients, 8 had an objective response to chemotherapy (response rate - RR- 34.7%, 95% confidence interval -CI- 14-55%) with 4 (17.4%) complete remissions (CRs) and 4 (17.4%) partial remissions (PRs). Survival: with a median follow-up of 8 months (range 1.5-25 months), one-year actuarial survival was 48% (95% CI 28-69%) and median survival was 47.8 weeks. CONCLUSION: Although the combination of topotecan and etoposide proved easy to administer on an outpatient basis with moderate and manageable toxicity, it showed only moderate activity as first-line chemotherapy in advanced SCLC.

Doubling epirubicin dose intensity (100 mg/m2 versus 50 mg/m2) in the FEC regimen significantly increases response rates. An international randomised phase III study in metastatic breast cancer. The Epirubicin High Dose (HEPI 010) Study Group.

PURPOSE: A phase III study was performed in patients with metastatic breast cancer (MBC) to evaluate the effect on response rate and survival of a doubling of the epirubicin dose intensity. PATIENTS AND METHODS: Four hundred fifty-six patients were randomised to receive either epirubicin 100 mg/m2 or 50 mg/m2 in combination with 5-FU (500 mg/m2) and cyclophosphamide (500 mg/m2) (FEC 100 vs. FEC 50) i.v., every 21 days for a maximum of six cycles (eight in case of CR). RESULTS: Of 456 patients, 390 were evaluable for efficacy. Objective response (CR + PR) was seen in 57% (FEC 100) vs. 41% (FEC 50) of the evaluable patients (P = 0.003). The CR rate was higher in the FEC 100 arm (12% vs. 7%, P = 0.07). FEC 100 produced significantly higher response rates in patients with visceral localisation (50% vs. 34%, P = 0.011) and in patients with more than two metastatic organ sites (64% vs. 37%, P = 0.001). Median time to progression (7.6 vs. 7 months) and overall survival (18 months vs. 17 months) were similar. Myelosuppression was the principal toxic effect, with grade IV neutropenia observed in 57% of the patients treated with FEC 100 vs. 9% of those on FEC 50. Grade IV infection or febrile neutropenia were observed in 8% (FEC 100) vs. 0.4% (FEC 50), but the incidence of septic death was the same in the two arms (two patients each). Cardiac toxicity was similar in the two treatment groups, with 5% vs. 3% of the patients taken off study due to cardiac events, primarily due to a decline in LVEF. Only three patients (two in FEC 100) experienced congestive heart failure. CONCLUSION: This trial shows that FEC with epirubicin at 100 mg/m2 can be administered for repeated cycles without bone marrow support with increased, though acceptable, toxicity and with a significant increase of antitumor effect (especially in visceral and/or high-burden disease), but no increased survival.

Morphometric grading of laryngeal squamous cell carcinomas.

The authors have used the point counting method for the morphometric assessment of the histological aspect of laryngeal carcinoma. The results suggest that subjective histopathological grading tends to overestimate the tumor grade. The implications of these data for the prediction of prognosis and selection of therapy are briefly discussed.