Phase I Dose-Escalation Study of Weekly Paclitaxel and Cisplatin Followed by Radical Hysterectomy in Stages IB2 and IIA2 Cervical Cancer.

Abstract

PURPOSE:

To define the optimal dose of paclitaxel combining cisplatin, as weekly neoadjuvant chemotherapy (NAC) for early-stage bulky squamous cell carcinoma of the uterine cervix.

METHODS:

A prospective trial was conducted for International Federation of Gynecology and Obstetrics stages IB2 and IIA2 cervical squamous cell carcinoma patients with magnetic resonance imaging or positron emission tomography-defined lymph node negative. Weekly fixed-dose cisplatin (40 mg/m) and 4-level dose escalation of paclitaxel (50, 60, 70, 80 mg/m) for 3 courses was given and followed by radical hysterectomy and pelvic lymph node dissection (RH-PLND) 14 to 28 days later. Postoperative adjuvant therapy was tailored according to pathologic response.

RESULTS:

No dose-limiting toxicity occurred. Twelve subjects were enrolled without reaching maximum tolerated dose, nor was any RH-PLND procedure delayed for >2 weeks. Pathologic response rate was 50% (complete in 2 and partial in 4). Paclitaxel dose level seemed unrelated to pathologic response. No subjects had grade ≥3 acute adverse events. Seven patients (58.3%) received postoperative radiotherapy or chemoradiation. Patients with human papillomavirus 16-negative tumor and aged 55 years and older had marginally higher risk (100%) of adjuvant radiotherapy or chemoradiation after NAC than those with human papillomavirus 16-positive or age less than 55 (P=0.081). With a median follow-up of 45.5 months, all 12 patients remained alive without disease.

CONCLUSIONS:

Weekly paclitaxel and cisplatin NAC for 3 courses can be tolerated with excellent short-term outcome. With the caveat of small number of patients, this study supports future phase II trials of weekly paclitaxel and cisplatin NAC for 4 to 5 cycles.

• Authors: Hung-Hsueh Chou, Huei-Jean Huang, Hao Lin, Lan-Yan Yang, Swei Hsueh, Feng-Yuan Liu, Yen-Lyin Liou, Jui-Der Liou, Min-Yu Chen, Angel Chao, Gigin Lin, Ting-Chang Chang, Chyong-Huey Lai
• Journal: American journal of clinical oncology (Am J Clin Oncol) Vol. 40 Issue 3 Pg. 241-249 (Jun 2017) ISSN: 1537-453X [Electronic] United States
• PMID: 25350466 (Publication Type: Clinical Trial, Phase I, Journal Article)

Chemical References

• Paclitaxel
• Cisplatin

Topics

• Adult
• Age Factors
• Aged
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects)
• Carcinoma, Squamous Cell (diagnostic imaging, pathology, therapy, virology)
• Chemoradiotherapy, Adjuvant
• Chemotherapy, Adjuvant
• Cisplatin (administration & dosage, adverse effects)
• Disease-Free Survival
• Female
• Human papillomavirus 16
• Humans
• Hysterectomy
• Lymph Node Excision
• Lymph Nodes (diagnostic imaging)
• Magnetic Resonance Imaging
• Middle Aged
• Neoadjuvant Therapy
• Neoplasm Staging
• Paclitaxel (administration & dosage, adverse effects)
• Papillomavirus Infections (complications, virology)
• Pelvis
• Positron-Emission Tomography
• Prospective Studies
• Radiotherapy, Adjuvant
• Tumor Burden
• Uterine Cervical Neoplasms (diagnostic imaging, pathology, therapy, virology)