Taxol carboplatin induction for head and neck cancer

Induction chemotherapy before chemoradiation is becoming standard for many types of head and neck cancer. This is because it allows sparing organs by performing a less extensive surgery on a smaller tumor after it had responded to chemotherapy or no surgery at all and overall effectiveness of treatment remains the same or better.

The role of chemotherapy and radiation for advanced head and neck cancer has evolved considerably over the last 20 years. Several studies, most prominently the Radiation Therapy Oncology Group (RTOG) study 91-11, which was undertaken in collaboration with the Head and Neck Intergroup and published in 2003, established the use of concurrent chemotherapy with radiation as the superior nonsurgical, larynx preservation strategy. The RTOG study demonstrated that patients with advanced laryngeal cancer receiving concurrent cisplatin and radiation had a better larynx preservation rate (84%) at a median follow-up of 3.8 years compared to that afforded either by radiation alone or by induction cisplatin/fluorouracil followed radiation (rates of 67% and 72%, respectively). This was confirmed by other studies.

Two large, randomized trials — the Veterans Affairs Laryngeal Cancer Study Group trial and a phase 3 trial conducted by the European Organization for Research and Treatment of Cancer (EORTC) — have demonstrated the benefit of induction chemotherapy with PF (100 mg/m2 of cisplatin on day 1 and 1000 mg/m2 of 5-FU by continuous infusion on days 1-5) with respect to organ preservation. In these trials, overall survival rates were similar in patients receiving either induction PF chemotherapy and radiation or surgery and radiation therapy. In patients with larger tumors that could not resected, PF induction therapy has been shown to produce long-term survival benefits, with overall survival times in a subset of inoperable patients receiving chemotherapy of 21% at 5 years and 16% at 10 years compared with 8% and 6%, respectively, in patients not receiving chemotherapy. In a phase 3 trial of neoadjuvant chemotherapy in patients with moth and pharyngeal cancer conducted by the French Groupe d’Etude des Tumeurs de la Tete et du Cou (GETTEC), the median overall survival time for patients with both resectable and unresectable tumors was 5.1 years when PF induction chemotherapy was followed by locoregional therapy vs 3.3 years for those who did not receive PF induction chemotherapy (P = .03).

Nonetheless, there have been strong and persistent undercurrents of interest in farther improving the induction chemotherapy for patients with locoregionally advanced head and neck cancer.  The standard neoadjuvant chemotherapy regimen has consisted of a platinum agent and 5-fluorouracil (5-FU), a regimen known as PF. More recently, the addition of a taxane such as docetaxel (or, less commonly, paclitaxel) to the PF regimen (a triple combination known as TPF) is emerging as a more effective and less toxic standard for induction chemotherapy. The potential for induction chemotherapy before concurrent treatment to improve survival, through patient selection or better disease control such as by reducing distant metastases, as well as to enhance larynx preservation while decreasing the morbidity of treatment, is of great interest. However, more data are needed before such sequential approaches, or as appears in this case, chemotherapy alone, can be promulgated as new treatment standards. The VA guidelines state: “Treatment options for stage III and IV (laryngela) patients include surgery plus postoperative radiation and induction chemotherapy followed by radiation”.
NCCN recommends both options, with induction or without but only lists the TPF regimen for induction.

In regard to using Taxol and carboplatin instead of TPF, a number of phase II trials suggest that it is a well tolerated and effective approach but the phase III trial did not confirm them. The Cancer and Leukemia Group B (CALGB) initially evaluated the combination of induction carboplatin and paclitaxel for two cycles followed by low-dose weekly concurrent chemotherapy with RT. They found a median survival time of 15.1 months, and the trial demonstrated the feasibility of this regimen]. A phase III trial, CALGB 39801, was then completed, in which all patients received low-dose weekly carboplatin and paclitaxel with concurrent RT to 66 Gy and were randomized to two cycles of induction chemotherapy. Both arms of that trial showed disappointing results, with a median survival time of 11–13 months, demonstrating that this was not an efficacious regimen.

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