présentées au 42ème meeting annuel de l’ASCO 2-6 Juin 2006 - Georgia World Congress Center Atlanta - Georgia - USA

A phase II trial of docetaxel and cisplatin combination in patients with locally advanced undifferentiated carcinoma of nasopharyngeal type (UCNT) : Study update

M. Yamouni, K. A. Benhadji, Y. Beldjilali, I. Lahfa, D. Yekrou, L. Djellali, M. Brahimi, K. Bouzid - CHU Oran, Oran, Algeria; Centre Pierre et Marie Curie, Algiers, Algeria.

Background : The standard treatment of locally advanced undifferentiated carcinoma of nasopharyngeal type (UCNT) is cisplatin based chemotherapy followed by locoregional radiotherapy. The purpose of this study is to assess the antitumor activity and toxicity of a new neoadjuvant chemotherapy regimen combining docetaxel (D) and cisplatin (C).

Patients and Methods : Previously untreated patients (pts) with histologically diagnosed locally advanced UCNT (Stages IVa and IVb TNM/UICC 1997) received D 75 mg/m2 and C 75 mg/m2 both on day 1, cycles were repeated every 21 days. Every pts received three cycles in a neoadjuvant setting before radiotherapy (4 to 6 weeks after the third cycle of DC). Pts were evaluated by clinical examination, CT scan of nasopharynx and nasofibroscopy with biopsy. Primary end point was tumor response. Secondary end points were disease free survival (DFS), toxicity and overall survival.

Results : 75 pts were enrolled in this trial, 54 males and 21 females with a median age of 41 years (range 18-69), WHO performance status of 0-1 in 71 pts and 2 in 4 pts. 19 pts had stage IVa and 56 pts had stage IVb. Toxicity, tumor response and survival over tree years were assessable in 75 pts. After 225 cycles, grade 3 & 4 toxicity (NCI-CTC 2.0) were: neutropenia (12%), febrile neutropenia (2%), anemia (1%), nausea and vomiting (23%), diarrhea (8%), mucositis (1%), reversible alopecia (70%). Two pts had onycolysis. Response rates for the 75 pts were: complete pathologic response 37% (28 pts), partial response 52% (39 pts), stable disease 8% (6 pts) and progression 3% (2 pts). The overall response rate was 89%. 74 pts (98%) had complete response after radiotherapy and one patient had stable disease. 31 patients had recurrence: 25 locoregional, and 6 metastatic (3 with bone metastasis, 2 hepatic metastasis and 1 cerebral metastasis). DFS and overall survival at 3 years were respectively 57% and 65%.

Conclusion : DC chemotherapy followed by radiation therapy is an effective regimen for the treatment of advanced UCNT. This treatment has an acceptable safety profile. These data need to be compared to concurrent chemoradiotherapy to assess the best strategy for the management of advanced UCNT.

Gemcitabine in metastatic breast cancer

A. Bensalem, K. Bouzid - Medical Oncology, Constantine, Algeria; CPMC, Algiers, Algeria.

Background : Gemcitabine (GEM) has shown efficacy in metastatic breast cancer (MBC). We conducted studies with GEM-based regimens to assess the efficacy and toxicity of GEM combined with other drugs in MBC. GEM was combined with docetaxel (DXL) in pre-treated MBC with an anthracycline-based regimen and GEM was combined with doxorubicin (DXR) in chemonaive patients (pts) with MBC. The studies' objectives were to show clinically relevant hematologic toxicity and response rates among pts treated with GEM-DXL either in combination in pre-treated pts with anthracycline regimen or GEM-DXR in chemonaive pts with MBC to assess the efficacy of GEM in MBC either in neoadjuvant or first-line treatment.

Methods : For GEM-DXL: 42 pts were enrolled; GEM: 1250 mg /m2 D1 & D8, DXL: 75 mg /m2 D1, every 21 days with classical premedication for DXL. For GEM-DXR: 51 pts were enrolled; GEM: 1250 mg /m2 D1 & D 8, DXR: 25 mg/m2 D1 & D8, every 21 days.

Results : See table below. In the GEM-DXR group, surgery was performed in 30 pts, and 13 (43.2%) had histologically complete response. The median TTP in this group was 13.3 months (range, 2-53).

Conclusions : GEM in MBC is very efficient and produced an interesting objective response and clinical benefit. This activity is consistent in either chemonaive pts or in pts with relapsing breast cancer.

Concurrent weekly cisplatin and radiation therapy for nasopharyngeal carcinoma

Y. Beldjillali, K. A. Benhadji, D. Yekrou, F. Dali Youcef, L. Djellali, M. Yamouni - CHU Oran, Oran, Algeria.

Background : Platimum based chemotherapy and radiotherapy combinations are the corner stone of management of nasopharyngeal carcinoma. Concomitant chemoradiotherapy may increase activity of the treatment but also increase toxicity. The purpose of the present study was to evaluate both aspects in patients (pts) with nasopharyngeal carcinoma (NPC).

Patients and Methods : : Previously untreated patients with NPC and ECOG performance status 0-2, were enrolled in this study. Cisplatin was administered weekly, starting on day 1 as an intravenous infusion at 40 mg/m2 together with radiation therapy: 1.8-2.0 Gy per fraction, 5 fractions a week. The total dose delivered to the nasopharynx was 65 to 70 Gy and 45 Gy to lymph nodes with a boost of 15 Gy the node-bearing areas. Treatments were administered during 6 weeks.

Results : 86 pts were enrolled in this study, 56 male and 30 female, with a median age of 41 years (range 16-69). 26 pts had stage IVb, 24 pts stage IVa, 17 pts stage III, 18 pts stage II and one pt stage I disease. 62 pts had undifferentiated, 22 poorly differentiated and 2 differentiated NPC. The complete response rate was 86% for all patients and the overall response rate was 93%, 7% of cases remained stable. After 494 cycles, grade 3 & 4 toxicity (NCI) were: neutropenia (1%), anemia (1%), nausea and vomiting (14%), dysphagia (12%). 4 pts had cutaneous induration/fibrosis. All pts presented hyposialosis. The disease free survival and overall survival at one year were 78% and 83% respectively.

Conclusions : Concomitant chemotherapy and radiotherapy in pts with NPC result in a high complete response rate with an acceptable safety profile. Further follow-up is necessary to assess the curative potential of this combined modality.

Gemcitabine/docetaxel (GD) versus gemcitabine/cisplatin (GC) in stage III/IV non-small cell lung cancer (NSCLC) : Preliminary results

M. Gamaz, T. Makhloufi, S. Taright, R. Baba-Ahmed, R. Amrane, K. Bouzid. CPMC, Algiers, Algeria;M Lamine Debaghine Hospital, Algiers, Algeria.

Background : This study was designed to compare the response rates and toxicities of the standard GC regimen versus GD, a non-platin regimen, in locally advanced and metastatic NSCLC.

Patients and Methods : : In both arms, gemcitabine 1250 mg/m2 was administered on days 1 and 8. In the GD arm, docetaxel 75 mg/m2 was given on day 8. In the GC arm, cisplatin 70 mg/m2 was given on day 1. Both regimens were repeated every 3 weeks

Results : From September 2004 to September 2005, 47 patients were enrolled In the GD arm (N = 25), the median age was 54.6 years (range, 45-70), and 22 (88.0%) were male. The majority of patients had either squamous cell (52.0%) or adenocarcinoma (44.0%), and stage IIIB disease (64.0%). In the GC arm (N = 22), the median age was 60.9 years (range, 42-74), and 20 (90.9%) were male. Most patients also had either squamous cell (50.0%) or adenocarcinoma (31.8%), and stage IIIB disease (59.1%). The difference in age between arms was significant (p = 0.046), but the differences in the remaining baseline characteristics and demographics were not significant. Toxicity and response results are in the table below.

Conclusions : Overall response rate was numerically higher in the GC arm than the GD arm, but the difference was not significant because of the small sample size in each arm. The toxicity profile was significantly better in the GC arm for fatigue and nausea/vomiting. We think that GC regimen will remain the standard in treatment for advanced and metastatic NSCLC; however, we will confirm these findings in a randomized phase II study.

Communication mise en ligne le 10 juillet 2006