Study Of Concurrent Chemoradiotherapy Research Articles

A Phase I Study of Concurrent Chemoradiotherapy with S-1 for T2N0 Glottic Carcinoma

Objective: Chemoradiation based on S-1, a novel oral antitumor agent of fluorinated pyrimidines, is the treatment for T2N0 glottic carcinoma; however, the optimal scheduling and dosing have still not been established. A phase I study was conducted to determine the maximum tolerated dose of S-1 with radiotherapy of 2 Gy/day for 5 days a week to a total dose of 60 Gy. Endpoints of this study were to examine the toxicity profile of this regimen and to determine the recommended dose of S-1. Methods: Concomitant administration with the above-mentioned radiotherapy of S-1 once a day for 2 weeks, beginning on the day therapy was started, followed by 2 weeks off the drug and 2 weeks on the drug with the dose escalating from S-1 60 mg/body (level 1) to 80 mg/body/day (level 2), and then to 100 mg/body/day (level 3). Results: Twenty-one patients were valid for safety. Eighteen patients were enrolled in the dose-escalation phase. In all patients, S-1 was administered. The maximum tolerated dose was determined to be 100 mg/body/day and the dose-limiting toxicity was indicated by the onset of grade 3 chemoradiation dermatitis. Therefore, the determined recommended dose of S-1 was 80 mg/body/day. Objective response according to Response Evaluation Criteria in Solid Tumors were observed in 20 of 21 patients who had measurable disease (95.2%). Conclusion: Concurrent S-1 and radiotherapy was feasible and well tolerated, and was suggested to produce a worthwhile response in T2N0 glottic carcinoma. These results warrant further investigation, and a phase II has already been started.

4538 POSTER Phase II study of concurrent chemoradiotherapy (CCRth) for bladder preservation in the treatment of muscle invasive bladder cancer

4538 POSTER Phase II study of concurrent chemoradiotherapy (CCRth) for bladder preservation in the treatment of muscle invasive bladder cancer

Chemoradiotherapy for Cervical Cancer: What Next?

In this issue, Lanciano et al report the results of the Gynecologic Oncology Group’s most recent randomized study of concurrent chemoradiotherapy for cervical cancer (GOG-165). This trial, which compared the results of radiation therapy delivered concurrently with either weekly cisplatin or protracted venous infusion of fluorouracil (FU), was closed well before the planned accrual goal of 416 patients and 150 events because a scheduled interim analysis suggested that patients treated with FU were not likely to have a better outcome than those treated with the control regimen of radiation and weekly cisplatin. Although this negative study does not represent a major advance in the treatment of patients with cervical cancer, it does highlight many of the issues and challenges faced by investigators who seek to improve cervical cancer treatment in the modern era. GOG-165 is best understood in its historical context. The trial was designed and opened in 1997. In that year, the GOG published abstracts describing encouraging preliminary results from GOG trials of cisplatin-based concurrent chemoradiotherapy. However, the inclusion of hydroxyurea in the control arms of these trials and other perceived weaknesses, including problems with the quality of radiation therapy, prevented clinicians from reaching an early consensus about the trials’ importance. Therefore, in an effort to consolidate earlier findings, GOG-165 was designed. The study initially was planned with three arms: a control arm of modern radiation therapy alone, a second arm intended to confirm the value of adding weekly cisplatin, and a third, experimental arm that consisted of treatment with radiation and protracted venous infusion FU. This third arm drew on extensive data demonstrating the value of FU-based chemoradiotherapy in patients with gastrointestinal neoplasms and was intended to follow-up on an inconclusive but encouraging Canadian study of concurrent radiation and protracted venous infusion FU in patients with cervical cancer. However, in 1999, just 18 months after GOG-165 was opened, the near-simultaneous publication of results from five prospective randomized trials, all of which demonstrated significant improvements in local control and survival with cisplatin-based chemoradiotherapy, led to a National Cancer Institute alert establishing chemoradiotherapy as a standard treatment for patients with locoregionally advanced cervical cancer. At that point, the GOG felt compelled to drop the radiationonly control arm of GOG-165 but continued to accrue patients to the two concurrent chemoradiotherapy arms. The results of GOG-165 suggest that radiation plus protracted venous infusion FU was not a better treatment than radiation plus weekly cisplatin, but it does not prove that FU is ineffective as a radiation sensitizer in patients with cervical cancer. More importantly, the study does not answer the potentially more interesting question of whether FU can enhance the beneficial effects of adding cisplatin to radiation therapy. In fact, although randomized trials have demonstrated the benefit of concurrent cisplatin and of concurrent cisplatin with FU, no trial has yet compared the two regimens directly. Although the GOG regimen of radiation plus weekly cisplatin tends to be favored by gynecologic oncologists in the United States, data from the seven randomized trials suggest that radiation plus a combination of cisplatin and FU might be more effective. Of four randomized trials that included radiation therapy plus weekly cisplatin, only one, reported by Keys et al in 1999, demonstrated a benefit for radiation therapy plus cisplatin over radiation therapy alone. In that study, patients with bulky stage IB cancers were randomly assigned to prehysterectomy radiation therapy or chemoradiotherapy. Two other trials—the current trial and the GOG three-arm trial published in 1999—did not have a control arm of radiation therapy only; instead, they included chemotherapy of uncertain value in the noncisplatin-containing JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 23 NUMBER 33 NOVEMBER 2

1040 POSTER Phase II study of concurrent chemoradiotherapy with capecitabine and cisplatin in patients with locally advanced squamous cell carcinoma of the head and neck

1040 POSTER Phase II study of concurrent chemoradiotherapy with capecitabine and cisplatin in patients with locally advanced squamous cell carcinoma of the head and neck

Phase I study of concurrent chemoradiotherapy (CRT) with S-1 and cisplatin (CDDP) in patients (pts) with unresectable locally advanced squamous cell carcinoma of head and neck (SCCHN)

5575 Background: An oral drug, S-1, composed of tegafur, 5-chloro-2, 4-dihydroxypyrimidine, and oxonic acid in a 1:0.4:1 molar ratio has shown high activity for head and neck cancer with a response rate of 34%. The aim of this study was to determine the maximum tolerated dose (MTD) of S-1 in combination with CDDP and radiotherapy. Methods: Eligibility: histologically proven SCCHN with unresectable locally advanced lesions, PS 0–1, age ≤ 75, adequate organ functions, and no prior chemotherapy. Chemotherapy consisted of administration of S-1 twice daily on days 1–14 at escalating doses of 40, 60, and 80 mg/m2/day, and 2-hour infusions of CDDP at 20 mg/m2/day on days 8–11, repeated twice with a 5-week interval. Once daily radiotherapy of 70 Gy in 35 fractions was given concurrently starting on day 1. Two additional cycles of S-1 and CDDP were planned 4 weeks after the completion of CRT. Dose-limiting toxicities were defined as neutropenic fever lasting for 4 days, grade (gr) 4 thrombocytopenia, and gr 3 non-hematological toxicities except mucositis, dysphagia, anorexia, nausea, vomiting, and infection due to mucositis. Results: Seventeen pts were enrolled. One pt did not receive CRT because of disease progression. Gr 2–3 stomatitis, dysphagia, neutropenia, dermatitis and xerostomia were the most frequently observed adverse events. The MTD was reached at 80 mg/m2/day of S-1, with 2 of 6 pts experiencing neutropenic fever lasting for 4 days. Of 7 pts treated at 60 mg/m2/day of S-1, one pt developed gr 3 diarrhea, and another developed neutropenic fever lasting for 2 weeks. For the latter, a diagnosis of myelodysplastic syndrome was made based on bone marrow analyses. Of the 16 pts treated with CRT, 12 experienced a complete response (CR) according to RECIST. Two additional pts who had residual neck lymph node metastasis underwent salvage neck dissection and pathological CR was confirmed. Conclusions: S-1 at 60 mg/m2/day for 14 days and CDDP at 20 mg/m2/day for 4 days are recommended for CRT. Although data are preliminary, the CR rate was very promising, and this approach warrants further investigation. No significant financial relationships to disclose.

A phase I study of concurrent chemoradiotherapy with docetaxel-cisplatin followed by docetaxel consolidation therapy in inoperable stage IIIA/B non-small cell lung cancer (NSCLC)

7350 Background: Docetaxel-based concurrent chemoradiotherapy (CTRT) regimens have shown promising activity and acceptable toxicity in stage IIIA/B NSCLC. This study was designed to evaluate the optimal therapeutic dose of docetaxel as consolidation therapy (DCT) after docetaxel-cisplatin CTRT. Methods: Patients (pts) with inoperable NSCLC, stage IIIA/B, received chemotherapy with docetaxel (20 mg/m2) and cisplatin (25 mg/m2) on days 1,8,15,22,29,36, with concurrent radiotherapy (5 days per week; 2 Gy per day) starting day 1 for a total dose of 66 Gy. If restaging after CTRT demonstrated disease stabilization or partial/complete response, then DCT with docetaxel (75 mg/m2, day 71 and 92) was added. DCT dose escalation to docetaxel 85 mg/m2 was planned for day 92, and a third docetaxel administration planned for day 113. Results: Of 23 patients enrolled (mean age 58.8±7.0 y), all were evaluable and had NSCLC stage IIIB; 6 and 17 patients had Eastern Cooperative Oncology Group performance status 0 and 1, re...

A phase I study of concurrent chemoradiotherapy with docetaxel-cisplatin followed by docetaxel consolidation therapy in inoperable stage IIIA/B non-small cell lung cancer (NSCLC)

7350 Background: Docetaxel-based concurrent chemoradiotherapy (CTRT) regimens have shown promising activity and acceptable toxicity in stage IIIA/B NSCLC. This study was designed to evaluate the optimal therapeutic dose of docetaxel as consolidation therapy (DCT) after docetaxel-cisplatin CTRT. Methods: Patients (pts) with inoperable NSCLC, stage IIIA/B, received chemotherapy with docetaxel (20 mg/m2) and cisplatin (25 mg/m2) on days 1,8,15,22,29,36, with concurrent radiotherapy (5 days per week; 2 Gy per day) starting day 1 for a total dose of 66 Gy. If restaging after CTRT demonstrated disease stabilization or partial/complete response, then DCT with docetaxel (75 mg/m2, day 71 and 92) was added. DCT dose escalation to docetaxel 85 mg/m2 was planned for day 92, and a third docetaxel administration planned for day 113. Results: Of 23 patients enrolled (mean age 58.8±7.0 y), all were evaluable and had NSCLC stage IIIB; 6 and 17 patients had Eastern Cooperative Oncology Group performance status 0 and 1, respectively. Partial response occurred in 10 pts, and 13 pts showed disease stabilization. 1 pt with a partial response had a complete tumor resection and left the study. No pts experienced disease progression. Median survival ± SD was 42.1 ± 24.3 weeks (18 pts are alive and under observation). The DCT dose was reduced to docetaxel 60 mg/m2 in all pts as the first 3 pts had grade 3/4 toxicity. Dose-limiting toxicities included grade 3 esophagitis and pneumonitis, observed in 26% and 13% of pts, respectively. Grade 3/4 hematologic toxicities were seen in 39% of pts. Grade 3 diarrhea and emesis occurred in 2 pts (9%). Conclusions: The optimal dose of docetaxel as consolidation therapy after CTRT is 60mg/m2. This regimen resulted in a high rate of tumor response in pts with good performance status. Schedule modifications are being studied as a result of observed toxicity with CTRT. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis Aventis Pharma

Dose-finding study of irinotecan and cisplatin plus concurrent radiotherapy for unresectable stage III non-small-cell lung cancer [seecomments

Irinotecan hydrochloride (CPT-11) shows marked anti-tumour activity alone and in combination with cisplatin in non-small-cell lung cancer (NSCLC). It is necessary to investigate combined-modality therapy including novel effective anti-cancer agents to improve long-term survival of patients with unresectable stage III NSCLC. A phase I/II study of concurrent chemoradiotherapy with CPT-11 and cisplatin was conducted to determine the maximum tolerated dose (MTD) and efficacy in this group of patients. Thirteen previously untreated patients with unresectable stage IIIA/B NSCLC were enrolled and efficacy and toxicity was evaluated in 12 of them; one patient was ineligible. Chemotherapy was repeated every 4 weeks for three courses. Radiation therapy was started on day 2 of the first course of chemotherapy and 60 Gy in 30 fractions was given over 6 weeks. Four of six patients enrolled at level 1 completed the scheduled treatment. Another two received only one and two courses of chemotherapy as a result of persistent leucopenia and neutropenic fever respectively. Three of six patients given level 2 therapy completed the scheduled treatment. Another three received only one and two courses of chemotherapy, two refused treatment because of diarrhoea and one died of pneumonia. Radiation therapy was inadequate in these three patients. As the CPT-11 dose intensity in this trial was low, because of the necessity of omitting CPT-11 administration on days 8 and/or 15 as a result of leucopenia or diarrhoea, and the low radiation therapy completion rate, the trial was discontinued at level 2. Five patients at level 1 and three at level 2 showed partial responses, an overall response rate of 67%. Although neither MTD nor dose-limiting toxicity could be identified, chemotherapy with CPT-11 and cisplatin plus concurrent radiation therapy was deemed unacceptable. We are now conducting a phase I/II study of chemotherapy using CPT-11 as a single agent in combination with radiation therapy.

Phase II study of concurrent chemoradiotherapy with use of uneven fractionation for the treatment of glioblastoma

Background A phase II one-arm study was performed to evaluate the efficacy and safety of concurrent chemoradiotherapy with the use of uneven fractionation in glioblastoma patients.