No abstract

Paclitaxel poliglumex (PPX), a macromolecule drug conjugate linking paclitaxel to polyglutamic acid, reduces systemic exposure to peak concentrations of free paclitaxel. Patients with non-small-cell lung cancer (NSCLC) who had received one prior platinum-based chemotherapy received 175 or 210 mg m À2 PPX or 75 mg m À2 docetaxel. The study enrolled 849 previously treated NSCLC patients with advanced disease. Median survival (6.9 months in both arms, hazard ratio ¼ 1.09, P ¼ 0.257), 1-year survival (PPX ¼ 25%, docetaxel ¼ 29%, P ¼ 0.134), and time to progression (PPX ¼ 2 months, docetaxel ¼ 2.6 months, P ¼ 0.075) were similar between treatment arms. Paclitaxel poliglumex was associated with significantly less grade 3 or 4 neutropenia (Po0.001) and febrile neutropenia (P ¼ 0.006). Grade 3 or 4 neuropathy (Po0.001) was more common in the PPX arm. Patients receiving PPX had less alopecia and did not receive routine premedications. More patients discontinued due to adverse events in the PPX arm compared to the docetaxel arm (34 vs 16%, Po0.001). Paclitaxel poliglumex and docetaxel produced similar survival results but had different toxicity profiles. Compared with docetaxel, PPX had less febrile neutropenia and less alopecia, shorter infusion times, and elimination of routine use of medications to prevent hypersensitivity reactions. Paclitaxel poliglumex at a dose of 210 mg m À2 resulted in increased neurotoxicity compared with docetaxel. (Jemal et al, 2007). For patients who present with advanced-stage disease (IIIb or IV), platinum-based multi-agent chemotherapy modestly improves survival compared with best supportive care or singleagent therapy (Pfister et al, 2004). However, nearly all patients relapse, and only 10 -20% survive 2 years. Three agents are currently approved for second-line therapy in advanced nonsmall-cell lung cancer (NSCLC). Docetaxel and erlotinib were approved on the basis of improved survival compared with best supportive care (Shepherd et al, 2000(Shepherd et al, , 2005. Pemetrexed received approval as second-line therapy due to its similarity in survival and response rates with lower toxicity than that of docetaxel, although statistical noninferiority was not achieved (Hanna et al, 2004). Despite response rates of approximately 10%, second-line treatment improves survival by approximately 2 months compared with best supportive care.Owing to the palliative nature of second-line therapy in NSCLC and its relatively modest effect on survival, minimising the toxicity of therapy is an important consideration. Additional effective therapies that achieve that goal are needed.Paclitaxel poliglumex (PPX) is a macromolecular polymer -drug conjugate that links paclitaxel to a biodegradable polymeric backbone consisting of L-glutamic acid residues. Because the conjugation site is through the 2 0 hydroxyl of paclitaxel, a site crucial for tubulin binding, conjugated paclitaxel does not interact with b-tubulin and is biologically inactive . Paclitaxel poliglumex is relatively stable in circulation; the ar...

Primary infusional ECF appears to be more active on clinical and histopathologic grounds than conventional chemotherapy for large operable breast cancer and is well tolerated. This approach now merits randomized comparison to determine if high CR rates may translate into improved survival.

No abstract

Postoperative chemotherapy is associated with improved survival compared with that after surgical intervention alone. Selected patients with completely resected non-small cell lung cancer should be offered chemotherapy.