Paclitaxel and gemcitabine in advanced non-nasopharyngeal head and neck cancer: A phase II study conducted by the Hellenic Cooperative Oncology Group

Background: Paclitaxel as monotherapy or in combination with other drugs has demonstrated significant activity in patients with squamous cell carcinoma of the head and neck region (SCCHN). Preclinical studies have shown gemcitabine to be highly active in SCCHN cell lines.Purpose of the study: To evaluate the activity and toxicity of the combination of paclitaxel by three-hour infusion and gemcitabine as first-line chemotherapy in patients with recurrent and/or metastatic head and neck cancer (HNC).Patients and methods: From September 1996 until May 1998, 44 patients with non-nasopharyngeal recurrent and/or metastatic HNC entered the study. There were 37 men and seven women with a median age of 61 years (range 35–79) and a median performance status of 1 (range 0–2). The location of the primary tumor in the majority of them was either the larynx or the oral cavity. Treatment consisted of six cycles of gemcitabine 1100 mg/m2 over 30 min on days 1 and 8 immediately followed on day 1 by paclitaxel 200 mg/m2 by three-hour infusion. The treatment was repeated every three weeks.Results: Twenty-four (55%) patients completed all six cycles of treatment. A total of 205 cycles were administered, 165 (81%) of them at full dose. The median relative dose intensity (DI) of gemcitabine was 0.93 and of paclitaxel 0.95. Except for alopecia, which was universal, grade 3–4 toxicities included neutropenia (21%), thrombocytopenia (5%), anemia (5%), infection (5%), flu-like syndrome (5%) and peripheral neuropathy (2%). Five (11%) patients achieved complete and 13 (30%) partial responses, for an overall response rate of 41%. After a median follow-up of 13 months, the median time to progression was four months and median survival nine months.Conclusions: The combination of paclitaxel and gemcitabine is active and well tolerated in patients with recurrent and/or metastatic HNC – randomized studies comparing this combination with other regimens are warranted.     

A prospective randomized phase III study in non-small-cell lung cancer comparing cisplatin, ifosfamide, vinblastine (VIP) versus cisplatin, ifosfamide and etoposide (VIP-16)

BACKGROUND:: It was recently reported that when ifosfamide was added to cisplatinand vinblastine the response rate was increased but not thesurvival in patients with non-small-cell lung cancer (NSCLC).The purpose of this study was to investigate the possibilityof increased responses and survival with use of the combinationof cisplatin, ifosfamide, etoposide (VIP-16) in comparison tothecombination of cisplatin, ifosfamide, vinblastine (VIP) in non-operableNSCLC. PATIENTS AND METHODS:: Two hundred twelve patients with histologically confirmed diagnosesof NSCLC were randomized into two groups: group A received cisplatin100 mg/ m², vinblastine 6 mg/m² and ifosfamide 3 mg/m² i.v.on day 1 every 3 weeks; group B received the same regimen exceptthat etoposide 120 mg/m² was substituted for vinblastine ondays 1, 2, and 3. Patients were well balanced for age, sex,performance status (PS), stage, grade, histology and sites ofdisease, and the relative dose intensity was similar in bothgroups. RESULTS:: One hundred one patients were evaluable for response in groupA and 99 in group B. The overall response rates were 29% ingroup A (5CR) and 25% in group B (3CR). The median time to progressionwas 7.51 (2–35) months for group A and 7.7(1–28)months for group B (P=0.34). The median survival was 8.49 (0.33–37.44)months for group A and 9.38 (0.43–36.59) for group B (P=0.39).Multivariate Cox stepwise analysis showed stage to be the onlysignificant prognostic factor for survival (P=0.0114). Toxicitywas not remarkable and not different between the two groupsexcept for alopecia which was much more common in the patientswho received etoposide. CONCLUSION:: VIP and VIP-16 combination chemotherapies are equally activein NSCLC with acceptable toxicity. Stage proved to be the mostsignificant prognostic factor for survival in this study. chemotherapy, cisplatin, NSCLC, randomized     

Induction Chemotherapy with Cisplatin, Epirubicin, and Paclitaxel (CEP), Followed by Concomitant Radiotherapy and Weekly Paclitaxel for the Management of Locally Advanced Nasopharyngeal Carcinoma

BACKGROUND: Clinical research on the treatment of nasopharyngeal cancer (NPC) has been focused primarily on the reduction of incidence of the development of distant metastases as well as the improvement of locoregional control. PATIENTS AND METHODS: Untreated patients with stage IIB-IVB nonmetastatic NPC were treated with three cycles of induction chemotherapy (IC) consisting of epirubicin 75 mg/m(2) followed by paclitaxel 175 mg/m(2) as 3-h infusion on day 1 and cisplatin 75 mg/m(2) on day 2 every 3 weeks, followed by concomitant radiation therapy (70 Gy), and chemotherapy (CCRT) with weekly paclitaxel 60 mg/m(2). RESULTS: From November 1999 until April 2003, 47 patients entered the study. Complete response rate post IC therapy was 15%, which was raised to 66% after the completion of CCRT. The most frequent side effect from IC was myelotoxicity (55%), whereas stomatitis and xerostomia were the most pronounced (grade 3, 4) toxicities during CCRT. The presence of Epstein-Barr virus (EBV) was detected either by in situ hybridization in tumor tissue sections or by polymerase chain reaction in the peripheral blood in 37 out of 46 patients tested (80%). All three histological types were associated with the presence of EBV. After a median follow-up of 23.5 months, median time to treatment failure was 17.9 months, whilst median survival has not been reached yet. CONCLUSION: IC followed by CCRT is feasible and produces durable complete responses in the majority of patients with NPC. The case detection rate of EBV in this study appears to be similar to that reported from endemically infected regions.     

XEL¿RI-bevacizumab versus FOLFIRI-bevacizumab as first-line treatment in patients with metastatic colorectal cancer: a Hellenic Cooperative Oncology Group phase III trial with collateral biomarker analysis

ABSTRACT: BACKGROUND: The aim was to compare two standard chemotherapy regimens combined with bevacizumab as first-line treatment in patients with metastatic colorectal cancer. METHODS: Patients previously untreated for metastatic disease were randomized in: group A (irinotecan, capecitabine, bevacizumab, every 3 weeks; XELIRI-bevacizumab) and group B (irinotecan, leucovorin, fluorouracil, bevacizumab, every 2 weeks; FOLFIRI-bevacizumab). Primary endpoint was progression-free survival (PFS). Plasma concentrations of nitric oxide, osteopontin, TGF-1 and VEGF-A were measured at baseline and during treatment. RESULTS: Among 285 eligible patients, 143 were randomized to group A and 142 to group B. Fifty-five patients (38.5%) in group A and 57 (40.1%) in group B responded (p=0.81). After a median follow-up of 42 months, median PFS was 10.2 and 10.8 months (p=0.74), while median OS was 20.0 and 25.3 months (p=0.099), for groups A and B, respectively. Most frequent grade 3-4 toxicities (group A vs group B) were neutropenia (13% vs 22%, p=0.053) and diarrhea (19% vs 11%, p=0.082). Baseline plasma osteopontin concentrations demonstrated prognostic significance for both PFS and OS. CONCLUSIONS: This trial did not show significant differences in efficacy between the groups. However, the toxicity profile was different. Baseline plasma osteopontin concentrations demonstrated independent prognostic significance. (Registration number: ACTRN12610000270011).     

Paclitaxel and gemcitabine versus carboplatin and gemcitabine in patients with advanced non-small-cell lung cancer. A phase III study of the Hellenic Cooperative Oncology Group.

BACKGROUND: This phase III study was designed to compare the combination paclitaxel (Taxol)-gemcitabine (PG) versus carboplatin-gemcitabine (CG) in patients with advanced inoperable non-small-cell lung cancer. METHODS: Chemotherapy-naive patients with performance status of zero or one were randomized to gemcitabine 1 gm/m(2) on days 1 and 8 plus either paclitaxel 200 mg/m(2) on day 1 (arm A) or carboplatin at an area under the concentration-time curve of 6 mg on day 1 (arm B) every 3 weeks. Primary end point was overall survival (OS). Secondary end points included objective response (OR), time to progression and toxicity. RESULTS: A total of 512 patients were enrolled and 452 eligible (arm A, 225; arm B, 227) were analyzed. All characteristics were well balanced with the exception of vena cava obstruction symptoms and lymph node involvement. Median survival was 9.97 months [95% confidence interval (CI) 8.74-12.0] for group A and 10.49 (95% CI 9.04-11.94) for group B. There was no difference in the OS, 1-year survival, OR and TtP. However, statistically significant differences were seen in toxicity. CONCLUSION: The two regimens are equally active. Myelotoxicity is worse in the CG group whereas alopecia, myalgia and neurotoxicity worse in the PG group.     

Long-term survival data and prognostic factors of a complete response to chemotherapy in patients with head and neck cancer treated with platinum-based induction chemotherapy: A hellenic co-operative oncology group study

A group of 154 patients with locally advanced head and neck cancer, treated with platinum-based induction chemotherapy, were followed up for 5 years and several pretreatment characteristics were analyzed for possible correlation to a complete response (CR) to chemotherapy, time to progression (TTP) and overall survival (OS). Clinical stage (p = 0.0125) were selected as important prognostic factors for CR by step-wise logistic regression. We also identified response to chemotherapy (p = 0.0120), age (p = 0.0066), clinical stage (p = 0.0363), N stage (p = 0.0028), and tumor grade (p = 0.0101) as significant prognostic variables for TTP. Response to chemotherapy (p < 0.0001) and age (p = 0.0017) were found also significant for OS. These long-term prognostic factors which retain their prognostic significance after several years of follow-up could be helpful in the design of future trials in this patient population. Med. Pediatr. Oncol. 28:401–410, 1997. © 1997 Wiley-Liss, Inc.     

Postoperative radiation and concomitant bolus fluorouracil with or without additional chemotherapy with fluorouracil and high-dose leucovorin in patients with high-risk rectal cancer: A randomized phase III study conducted by the Hellenic Cooperative Oncology Group

Background: Randomized studies have shown that postoperative chemotherapy with or without radiation therapy (RT) improved local control and survival of patients with stages II or III rectal cancer. However, the optimal sequence of treatments and the optimal chemotherapeutic regimen have not been defined. Modulation of fluorouracil (FU) by leucovorin (LV) has yielded a highly significant difference in response rate from that of FU monotherapy, as suggested by an overview of randomized trials in patients with advanced colorectal cancer. However, this difference in response rate did not translate into a survival benefit.Purpose: To evaluate the impact on the disease-free survival (DFS) and overall survival (OS) of patients with stages II or III rectal cancer of postoperative RT and concomitant bolus FU administration alone or with additional chemotherapy using FU and high-dose LV.Patients and methods: From October 1989 until February 1997, 220 patients were randomized postoperatively to receive either one cycle of chemotherapy with FU (600 mg/m²/week × 6 followed by a two-week rest) and leucovorin (LV, 500 mg/m²/week × 6 as a two-hour infusion) followed by pelvic RT with concomitant FU (400 mg/m²) as a rapid intravenous injection during the first three and last three days of RT, and three more cycles of the same chemotherapy with FU and LV (standard, group A, 111 patients) or pelvic RT with concomitant FU only (experimental, group B, 109 patients).Results: As of August 1998, after a median follow-up of 4.9 years, there was no significant difference in either three-year DFS (Group A, 70.3%; group B, 68.2%, P = 0.53) or OS (group A, 77%; group B, 73.3%, P = 0.75). Cox multivariate analysis revealed stage of disease, number of infiltrated nodes, tumor grade, presence of regional implants and perforation to be significant prognostic factors. The incidence of severe side effects was significantly higher in the patients in group A than in those in group B (32.4% vs. 4.6%, P < 0.0001).Conclusions: The incorporation of additional chemotherapy with FU and LV into postoperative concomitant RT and bolus infusion of FU does not offer a 10% three-year survival benefit over that of concomitant RT and bolus infusion of FU, and significantly increases toxicity in patients with stages II or III rectal cancer.