A randomized controlled phase II trial of a novel composition of paclitaxel embedded into neutral and cationic lipids targeting tumor endothelial cells in advanced triple-negative breast cancer (TNBC).

BACKGROUND: EndoTAG-1, composed of paclitaxel embedded in liposomal membranes targeting tumor endothelial cells, was evaluated for safety and efficacy in advanced triple-negative breast cancer (TNBC). PATIENTS AND METHODS: One hundred and forty patients were treated with weekly EndoTAG-1 (22 mg/m(2)) plus paclitaxel (70 mg/m(2)), twice weekly EndoTAG-1 (2× 44 mg/m(2)), or weekly paclitaxel (90 mg/m(2)) for greater than or equal to four cycles (3-week treatment + 1-week rest) or until progression/toxicity. Primary end point was progression-free survival (PFS) rate evaluated centrally after four cycles of therapy (week 16). The study was not powered for intergroup comparisons. RESULTS: The PFS rate at week 16 was 59.1% [one-sided 95% CI: 45.6, ∞] on combination treatment, 34.2% [21.6, ∞] on EndoTAG-1, and 48.0% [30.5, ∞] on paclitaxel. Median PFS reached 4.2, 3.4, and 3.7 months, respectively. After complete treatment (week 41 analysis), median overall survival (OS) was 13.0, 11.9, and 13.1 months for the modified Intention-to-Treat (ITT) population and 15.1, 12.5, and 8.9 months for the per-protocol population, respectively. The clinical benefit rate was 53%, 31%, and 36% for the treatment groups. Safety analysis revealed known toxicities of the drugs with slight increases of grade 3/4 neutropenia on combination therapy. CONCLUSION: Treatment of advanced TNBC with a combination of EndoTAG-1 and standard paclitaxel [Taxol® (Bristol-Myers Squibb GmbH), or equivalent generic formulation] was well tolerated and showed antitumor efficacy. The positive trend needs to be confirmed in a randomized phase III trial. STUDY REGISTRATION: European Clinical Trials Database: EudraCT number 2006-002221-23. ClinicalTrials.gov identifier: NCT00448305.

Neoadjuvant chemotherapy with ifosfamide and cisplatin combination in advanced head and neck cancer: a retrospective analysis of 519 patients: a single institution experience.

Advanced head and neck cancer is a major therapeutic problem in India. Ifosfamide has shown significant activity as a single agent in head and neck squamous carcinoma. In this study, we present our experience with two cycles of ifosfamide and cisplatin in the neoadjuvant setting given to a total of 519 patients. The complete response rate was 20% and the overall response rate was 80%. The treatment was well tolerated, there was no need for dose reduction, and there were no life-threatening side effects. We feel that this high response rate is sufficient to warrant more studies using ifosfamide-based combinations in a neoadjuvant setting for squamous carcinoma of the head and neck.

Two- vs three-drug combination chemotherapy in advanced or recurrent head and neck cancer: a single institution experience of 361 patients.

Head and neck squamous cancer is a major concern in India. The proportion of advanced cases is significantly high, and these patients have dismal survival prospects despite aggressive therapy. Often surgical resection and/or radiotherapy are not feasible in these patients. Hence, we decided to explore the option of neoadjuvant chemotherapy using effective agents like ifosfamide and paclitaxel in combination with cisplatin in these patients. A total of 361 patients were evaluable at the end of study. Of these, 207 had received ifosfamide and cisplatin and 154 had received taxanes (paclitaxel or docetaxel) in addition to ifosfamide and cisplatin. The ifosfamide-cisplatin group had an overall response rate of 66.67% (CR, 16.42%; PR, 50.24%) and the median duration of response was 5.5 mo; whereas the group in which taxanes were added, showed an overall response rate of 73.37% (CR, 7.79%; PR, 65.58%) with a median duration of response of 10 mo. The toxicity in both the groups was acceptable and there was no mortality. We conclude that taxane-based combinations have a significant activity in advanced head and neck squamous cancer and warrant further studies.