Results of a European Organization for Research and Treatment of Cancer/Early Clinical Studies Group phase II trial of first-line irinotecan in patients with advanced or recurrent squamous cell carcinoma of the cervix.
ABSTRACT To determine the efficacy and tolerability of irinotecan (CPT-11) in advanced or recurrent cervical carcinoma.
Eligible patients had histologically confirmed, inoperable, progressive, metastatic or recurrent squamous cell cervical carcinoma and had received no radiotherapy in the preceding 3 months and had never received chemotherapy. The initial irinotecan dosage of 350 mg/m(2) every 3 weeks was modifiable according to toxicity. Treatment continued for six cycles after complete response, or until disease progression or excessive toxicity after partial response, or for three additional cycles in the case of stable disease. Patients were stratified into group A (>/= one measurable lesion in a previously unirradiated area, with or without progressive disease in irradiated fields) or group B (measurable new lesion[s] in an irradiated field).
Fifty-one of 55 enrolled patients were eligible for inclusion (median age, 47 years; range, 30 to 71 years). The response rate was 15.7% (95% confidence interval [CI], 7.0% to 28.6%) overall, 23.5% (95% CI, 10.7% to 41.2%) for group A (complete response, 2.9%), and zero for group B. The median time to progression and median survival were 4.0 and 8.2 months for group A and 2.5 and 4.2 months for group B, respectively. The major grade 3/4 toxicities for groups A and B were diarrhea (24.3% and 55.5%, respectively) and neutropenia (24.3% and 33.3%, respectively). There were four toxicity-related deaths, three in group B. Patients with no prior external pelvic irradiation experienced fewer grade 3 and 4 adverse events.
Irinotecan is effective in treating cervical squamous cell carcinoma if disease is located in an unirradiated area. Because of toxicity, a reduced dose is advised for patients previously treated with external pelvic irradiation.
SourceAvailable from: Jan B Vermorken[Show abstract] [Hide abstract]
ABSTRACT: 2 ABSTRACT A review is given of the standard approaches in the management of patients with newly diagnosed and recurrent cervical cancer. New directions in treatment are discussed. They focus on the following topics: the usefulness of short and dose intensive single-agent cisplatin regimens, the role of hyperthermia in combination with chemotherapy and/or radi- ation therapy, the availability of some interesting new cytoto- xic agents, recent outcomes of some combined modality stu- dies in high-risk patients, and the role of hemoglobin levels at the time of treatment. It is concluded that further improve- ment in radiotherapy techniques will be a major challenge. Chemoradiation is considered the new standard for high-risk patients, who in the past would have been treated with radia- tion therapy alone. The preferred chemotherapy regimen for that purpose is single-agent cisplatin given at a dose of 40 mg/m 2 /week. Attention should be given to the usefulness of hyperthermia in combination with radiation therapy, chemo- therapy or both. Moreover, further study is needed with agents with a stronger radio-enhancement potential, while maneuvers to maintein normal levels of tumor oxygenation should be an important component of therapy. Neoadjuvant chemotherapy followed by radiotherapy for the treatment of patients with locally advanced cervical cancer cannot be re- commended, but its use prior to surgery needs to be further explored. Uncertainty about the potential role of adjuvant chemotherapy remains. Quality of life issues should be high on the list of priorities when treating patients with recurrent disease.
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ABSTRACT: The use of taxanes in the treatment of gynecologic malignancies has expanded tremendously over the past 30 years. Both paclitaxel and docetaxel have unique microtubule stabilizing, antiangiogenic and radiation sensitizing properties that endow them with remarkable activity as chemotherapeutic agents. As research into the appropriate dose, timing, treatment interval, and response rates have been studied, they have emerged as one of the most active agents available in the treatment of gynecologic cancer. The body of research on taxanes continues to expand especially with regard to the use of taxanes in alternative formulations and in combination with newer treatments or routes of treatment. This review focuses on the development of taxanes as an effective therapy in the treatment of gynecologic cancers and data currently available in the literature regarding their efficacy. Future directions of taxane-based chemotherapy with regards to ovarian, uterine, and cervical cancers are also addressed. There is little doubt that taxane-based chemotherapy will remain an integral part of the treatment of gynecologic cancer for the foreseeable future.Anti-cancer drugs 12/2013; DOI:10.1097/CAD.0000000000000057 · 1.89 Impact Factor
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ABSTRACT: Objective: We compare different dosimetric parameters in cervical cancer patients receiving concurrent chemotherapy and three-dimensional conformal radiotherapy (3DCRT) or intensity-modulated radiation therapy (IMRT) and explore the incidence of hematological toxicity (HT) in these patients. Methods: Twenty patients receiving 3DCRT or IMRT and 4 weekly doses of cisplatin (25 mg/m(2)/w) were studied. The volumes of bone marrow receiving 10, 20, 30, 40 and 50 Gy or greater (V10, V20, V30, V40, and V50, respectively) were calculated. The HT was graded according to the guidelines of the Radiation Therapy Oncology Group system. The associations between dosimetric parameters and HT and chemotherapy delivery were analyzed. Results: The bone marrows V30, V40, and V50 were lower in the IMRT group than in the 3DCRT group (62.93% vs 76.91%, 31.36% vs 39.60%, and 9.79% vs 15.44%, respectively). No statistical difference was observed for both V10 and V20. Acute hematologic toxicity occurred in both groups but was more frequent in the 3DCRT group. The percentage of patients with grade 2 and worse leukopenia and neutropenia was 90% and 80% in the 3DCRT group, whereas it was 80% and 40% in the IMRT group. The median nadir of white blood cells and the absolute neutrophil count were significantly lower in the 3DCRT group than in the IMRT group (1.96 x 10(9) vs 2.72 x 10(9) and 1.09 x 10(9) vs 1.86 x 10(9), respectively). Conclusion: The IMRT reduced the volume of bone marrow irradiated at the higher doses and the incidence and severity of acute hematologic toxicity in cervical cancer patients undergoing concurrent chemoradiotherapy.International Journal of Gynecological Cancer 10/2014; 24(9). DOI:10.1097/IGC.0000000000000292 · 1.95 Impact Factor