Concurrent chemoradiotherapy in locoregionally recurrent nasopharyngeal carcinoma

PURPOSE: To analyze the results of concurrent chemoradiotherapy in patients with locoregional recurrent nasopharyngeal carcinoma. METHODS AND MATERIALS: We performed a retrospective analysis of 35 patients with locoregional recurrent nasopharyngeal carcinoma referred to our department between March 1994 and November 2002. Most patients were male (77%), Chinese (97%), and had undifferentiated carcinoma (89%). Most had extensive locally recurrent Stage rT3-T4 disease (66%) with a median age at recurrence of 49 years (range, 35-69 years). A repeat course of radiotherapy was given concurrently with cisplatin, with cisplatin/5-fluorouracil as consolidation treatment. Significant morbidities were present, including cranial nerve palsies due to extensive recurrent local disease before treatment of the recurrence. RESULTS: The response rate to concurrent chemoradiotherapy was 58% (29% complete response and 29% partial response). The 5-year progression-free and overall survival rate, calculated using the Kaplan-Meier method, was 15% and 26%, respectively. Only 3 patients developed systemic metastases. Grade 3-4 acute toxicities included emesis (9%) and neutropenia (14%), and Grade 3-4 late toxicities consisted of temporal lobe necrosis (3%), cranial neuropathy (6%), and endocrine abnormalities (14%). CONCLUSION: Concurrent chemoradiotherapy is feasible in a selected group of patients with locoregional recurrent NPC, but the risk of major late toxicities is significant.     

Docetaxel and cisplatin: An active regimen in patients with locally advanced, recurrent or metastatic squamous cell carcinoma of the head and neck

Background: Docetaxel and cisplatin are among the most active antitumor agents in head and neck cancer, and phase I studies found the combination of the two drugs to be feasible. The EORTC ECSG performed a multicenter phase II study in patients with locally advanced, recurrent or metastatic squamous cell carcinoma of the head and neck to evaluate the antitumor efficacy and toxicity of this combination.Patients and methods: Eligibility criteria included written informed consent, a WHO performance status <2, life expectancy of >12 weeks, and adequate bone marrow, liver and renal function. Neoadjuvant pretreatment with cisplatin-based chemotherapy or prior radiotherapy were allowed. Patients were ineligible if pretreated with taxoids, had CNS involvement, concurrent malignancy, peripheral neuropathy, or no measurable disease. Treatment consisted of docetaxel 100 mg/m2 (one-hour i.v. infusion), followed by cisplatin 75 mg/m2 (three-hour i.v. infusion), repeated every three weeks. Supportive care included hydration, 5HT3- antagonists, and corticosteroids.Results: Forty-four patients (median age 55 years, range 35–76) entered the trial; 41 patients were eligible, 164 cycles of treatment were evaluable for toxicity, and 31 patients for response. Fourteen patients had undergone prior surgery, 15 had received radiotherapy, and five had had chemotherapy. A median number of four treatment cycles (range 1–6) was given. Hematologic and non-hematologic toxicities were common, but hypersensitivity reactions and fluid retention were very infrequent due to corticosteroid prophylaxis. Four patients were taken off the study due to toxicity, and one toxic death occurred due to pneumonia. Among 41 eligible patients, objective responses as confirmed by independent review included six complete remissions and 16 partial remissions, resulting in an overall response rate of 53.7% (95% confidence interval: 37.4%–69.3%). Responses occurred in locally advanced, recurrent and metastatic disease, both in pre- and non-pretreated patients. Of 22 evaluable, non-pretreated patients with locally advanced or metastatic disease, five achieved complete responses, and 14 partial responses. Observed among nine evaluable pretreated patients with locally advanced or metastatic head and neck cancer were one complete response and two partial responses.Conclusion: The combination of docetaxel and cisplatin is feasible and active in locally advanced, recurrent, and metastatic squamous cell carcinoma of the head and neck.     

Sequential methotrexate and 5-fluorouracil with bleomycin and cisplatin in the chemotherapy of advanced squamous cancer of the head and neck

A bolus intravenous dose of 5-fluorouracil of 600 mg/M2 was added exactly 1 hour after methotrexate administration in an established combination program including bleomycin and cisplatin for advanced squamous cell cancer of the head and neck. Results were no better than those observed previously with the three drugs, and hematologic and mucosal toxicities were slightly worse. The overall response rate was 41% in 34 patients with recurrent or metastatic disease, with only 6% complete remissions. Median time to disease progression for responding patients was 14 weeks, compared with 10 weeks for nonresponders. Partial response had little impact on survival. Among 12 patients with far-advanced disease confined above the clavicles without prior radiotherapy, 9 (75%) achieved partial remission, but the median survival, even with later surgery or irradiation, was only 34 weeks.     

Phase I-II study of cisplatin, VP-16, MGBG, mitomycin, and vinblastine with radiation therapy for non-small-cell lung cancer

Nineteen patients with locoregional non-small-cell lung cancer (NSCLC) were treated with two courses of cisplatin/VP-16/MGBG, followed by involved field radiotherapy and, subsequently, the same chemotherapy alternating with mitomycin-C/vinblastine. Five of 17 patients obtained a response (CR + PR) after induction chemotherapy. Following radiotherapy, an additional two patients responded. The median survival was 7.5 months, with the two longest survivors at 30 and 32 months. Hematologic toxicity was severe, with two deaths from severe neutropenia. Renal and gastrointestinal toxicities were moderate. This program of aggressive therapy did not increase the response rate or median survival compared with those of comparable patients treated in recent trials using radiotherapy alone or combined radiotherapy plus chemotherapy.     

A phase II study of cisplatin, vindesine and continuously infused 5-fluorouracil in the treatment of advanced non-small-cell lung cancer. Osaka Lung Cancer Chemotherapy Study Group.

Fifty-two previously untreated patients with advanced non-small-cell lung cancer (NSCLC) were treated on a 14 day cycle with cisplatin (60 mg m-2 i.v.) and vindesine (3 mg m-2 i.v.) on day 1, followed by a 3 day continuous infusion of 5-fluorouracil (800 mg m-2 day-1) starting on day 8. An overall response rate of 40.4% was observed in 47 evaluable patients, which included one complete response and 18 partial responses. Responses were achieved in 61.1% of stage 3 patients and 27.6% of stage 4 patients. The median progression-free interval was 19.3 weeks, and median survival time was 41.6 weeks (47.1 weeks for patients with stage 3 disease and 38.7 weeks for those with stage 4 disease). Toxicity was well tolerated. Gastrointestinal and renal toxicities did not exceed WHO grade 2. Grade 3 or 4 leucopenia and anaemia occurred in nine (19%) and four (9%) patients respectively, but only grade 2 thrombocytopenia was observed. Phlebitis at the infusion site was observed in 24 patients (53%). This treatment programme achieved a response rate similar to other active combination regimens for the treatment of advanced NSCLC, and was less toxic.     

A phase II trial of combination of CPT-11 and cisplatin for advanced non-small-cell lung cancer. CPT-11 Lung Cancer Study Group.

A phase I trial of the combination of irinotecan (CPT-11) with cisplatin in advanced non-small cell lung cancer (NSCLC) showed a very promising response rate of 54% in previously untreated NSCLC patients. This study was conducted to confirm the activity and toxicities of CPT-11 and cisplatin combination for previously untreated NSCLC in a multi-institutional phase II study. Seventy patients with stage IIIB or IV NSCLC received CPT-11 60 mg m(-2) intravenously (i.v.) on days 1, 8 and 15, and cisplatin 80 mg m(-2) (i.v.) on day 1 every 4 weeks. Assessments were made of response, survival and toxicities. Sixty-nine were eligible, and evaluable for toxicities and survival, and 64 patients evaluable for response. Thirty-three patients (52%; 95% confidence interval 39-64%) achieved an objective response, with one complete response (2%) and 32 partial responses (50%). The median duration of response was 19 weeks and the overall median survival time was 44 weeks. The 1-year survival rate was 33%. The major toxic effects were leucopenia and diarrhoea. Grade 3 or 4 leucopenia, neutropenia, and diarrhoea occurred in 32 patients (46%), 53 patients (80%), and 13 patients (19%) respectively. A combination of CPT-11 and cisplatin is very effective against non-small-cell lung cancer with acceptable toxicities.     

Combined chemotherapy for recurrent and metastatic nasopharyngeal carcinoma

Thirty-two patients (24 males, 8 females; median age 54 yrs) with recurrent and/or metastatic undifferentiated carcinoma of the nasopharyngeal type were treated with chemotherapy. Remissions were observed in 17 of 32 (53.2%) with 5 complete (CR) (15.6%) and 12 partial responses (PR) (37.6%). A combination of cisplatin and 5-fluorouracil was the most effective regimen (CR + PR = 83.3%). Objective responses. (CR + PR) were 47% (CR = 11.7%) in schemes without cisplatin and 60% (CR = 20%) in cisplatin-based combinations. The median overall duration of response was 7.2 months. The median overall survival time was 10.3 months: 15.1 months for responders and 5.2 for non-responders. No important toxicity was observed.     

Cisplatin and 5-fluorouracil in refractory breast cancer patients: A phase II study

Summary 24 patients with a median of 3 prior chemotherapy regimens were treated in our department with cisplatin 20 mg/m² (with pre- and posthydration) and 5-fluorouracil 200 mg/m² i.v. on day 1–5, every three weeks. 23 patients are evaluable; one had early death. 4 patients (17%) achieved a partial response, 8 had stable disease, and 11 progressed. Toxicity observed was moderate and no renal toxicity was noted. This study therefore shows tolerable toxicity but limited usefulness of adding cisplatin to 5-fluorouracil according to this schedule in these highly pretreated patients.     

Resectable gastric carcinoma. An evaluation of preoperative and postoperative chemotherapy

Patients with locoregional gastric carcinoma often die because of the low rates of curative resection and frequent appearance of distant metastases (mainly peritoneal and hepatic). To evaluate the feasibility of preoperative and postoperative chemotherapy, 25 consecutive previously untreated patients with potentially resectable locoregional gastric carcinoma received two preoperative and three postoperative courses of etoposide, 5-fluorouracil, and cisplatin (EFP). Ninety-eight courses (median, five courses; range, two to five courses) were administered. Six patients had major responses to EFP. Eighteen patients (72%) had curative resections, and three specimens (12%) contained only microscopic carcinoma. At a median follow-up of 25 months, the median survival of 25 patients was 15 months (range, 4 to 32+ months). Peritoneal carcinomatosis was the most common indication of failure. One patient died of postoperative complications, but there were no deaths due to chemotherapy. EFP-induced toxic reactions were moderate. Preoperative and postoperative chemotherapy for locoregional gastric carcinoma is feasible, and additional studies to develop regimens that could result in 5% to 10% complete pathologic responses may be warranted.     

Eastern Cooperative Oncology Group phase II trial (E4296) of oral 5-fluorouracil and eniluracil as a 28-day regimen in metastatic colorectal cancer

Coadministration of eniluracil with 5-fluorouracil (5-FU) allows the oral absorption of small doses of 5-FU, resulting in therapeutic plasma levels. A phase II clinical trial of this combination using a continuous dosing schedule was carried out in patients with metastatic colorectal cancer. Fifty-three previously untreated patients and 46 patients who had received one prior regimen for metastatic disease were enrolled. Patients received 10 mg/m2 of eniluracil and 1 mg/m2 of 5-FU twice daily for 28 days, with cycles repeated after a 7-day rest until progression of disease or prohibitive toxicity. Seven of 53 previously untreated patients had an objective tumor response (13.2%): 1 complete response and 6 partial responses. The mean duration of response was 6.3 months. Only 1 of the 45 evaluable patients in the previously treated group had a partial response, with no complete responses. The duration of response was 3 months. The median progression-free survival was 3.4 months for the previously untreated group and 2.5 months for the previously treated group. Median overall survival was 11.1 months for the previously untreated group and 9.0 months for the previously treated group. Hematologic toxicity was infrequent, with 3 patients experiencing grade 3 toxicity. Incidence of grade 3/4 toxicity included 11 patients with diarrhea, 5 with nausea, and 4 with vomiting. Other common toxicities included anemia and stomatitis, but they were generally mild. This regimen is well tolerated and shows activity in previously untreated patients with metastatic colorectal cancer that is similar to that observed with other 5-FU-based regimens. This regimen has not shown to be effective in patients who have had prior chemotherapy.     

Phase II trial of carboplatin plus cisplatin in recurrent and advanced squamous cell carcinoma of the head and neck

Cisplatin is one of the most active chemotherapeutic agents for the treatment of squamous carcinoma of the head and neck; however, neurotoxicity and nephrotoxicity are dose-limiting. The analog, carboplatin, is a promising new agent with similar activity but a different spectrum of toxicity. To evaluate if a therapeutic advantage could be achieved with acceptable toxicity, a combination of carboplatin 350 mg/m2 and cisplatin 50 mg/m2 were administered every 28 days to patients with recurrent or metastatic disease who had received no prior chemotherapy. Of 24 patients enrolled in this study, 21 were assessable for response and toxicity. Five partial responses were observed (24%; 95% confidence interval [Cl], 4.9% to 38.6%). No complete response occurred. Two of these patients received definitive radiotherapy and achieved complete responses. The median survival of all patients was 24 weeks. Hematologic toxicity was dose-limiting necessitating a decrease in the starting dose of carboplatin to 300 mg/m2. Nonhematologic toxicity was infrequent and mild. Significant renal impairment occurred in only two patients. Although treatment with the combination of carboplatin and cisplatin is feasible, we found no therapeutic advantage in terms of an increased response or survival.     

Three-week schedule of irinotecan plus cisplatin in patients with previously untreated extensive-stage small-cell lung cancer

Irinotecan and cisplatin demonstrated promising outcomes in extensive-stage small-cell lung cancer. According to the dosage and schedule of irinotecan, efficacy and toxicity profiles showed subtle differences. This study was designed to evaluate efficacy and toxicity of 3-week schedule of irinotecan/cisplatin in patients with previously untreated extensive-stage small-cell lung cancer. The primary objective was to evaluate response rate and secondary objectives were overall survival and progression-free survival. Patients with previously untreated extensive-stage small-cell lung cancer were enrolled. Irinotecan 65 mg m-2 was administered on days 1 and 8 and cisplatin 60 mg m-2 on day 1. Treatment was repeated every 3 weeks. Seven out of 54 patients (13.0%) had complete response, and partial response was observed in 33 (61.1%). The overall response rate was 74.1% (95% CI; 62.0-82.2%). Stable disease was observed in eight (14.8%) and no progressive disease was observed. After a median follow-up duration of 28.7 months, the median overall survival and progressive-free survival were 13.6 and 6.5 months, respectively. Major grade 3/4 toxicities were neutropenia (50.0%), anorexia (42.6%), diarrhoea (29.6%), fatigue (29.6%) and vomiting (13.0%). There was one treatment-related death owing to pneumonia. Three-week schedule of irinotecan/cisplatin showed effective antitumour activity and moderate toxicities in patients with previously untreated extensive-stage small-cell lung cancer.     

Combined Chemotherapy for Recurrent and Metastatic Nasopharyngeal Carcinoma

Summary

Thirty-two patients (24 males, 8 females; median age 54 yrs) with recurrent and/or metastatic undifferentiated carcinoma of the nasopharyngeal type were treated with chemotherapy. Remissions were observed in 17 of 32 (53.2%) with 5 complete (CR) (15.6%) and 12 partial responses (PR) (37.6%). A combination of cisplatin and 5-fluorouracil was the most effective regimen (CR + PR = 83.3%). Objective responses. (CR + PR) were 47% (CR=11.7%) in schemes without cisplatin and 60% (CR = 20%) in cisplatin-based combinations. The median overall duration of response was 7.2 months. The median overall survival time was 10.3 months: 15.1 months for responders and 5.2 for non-responders. No important toxicity was observed.     

Chemotherapy for paranasal sinus carcinoma. A 10-year experience at Wayne State University

The role of chemotherapy in the management of patients with cancer of the paranasal sinus has not been defined. An analysis of 24 evaluable patients treated with chemotherapy as part of their overall therapy was performed. There were 16 male patients and eight female patients. Sixteen patients were previously untreated and eight had recurrent disease after surgery and/or radiotherapy. Six of the previously untreated patients had metastatic disease on presentation (four central nervous system (CNS) and two lung), and four recurrent patients had CNS involvement. The majority of patients (78%) had squamous cell carcinoma. The chemotherapy regimens included cisplatin (CDDP), vincristine (VCR), and bleomycin (COB), 5-fluorouracil (5-FU) infusion and CDDP, or 5-FU/CDDP and methotrexate (MTX). All patients had computed tomography (CT) measurable disease. Previously untreated patients underwent surgery and/or radiotherapy postchemotherapy. The overall response rate to chemotherapy for previously untreated patients was 82% (complete response [CR] 44%, partial response [PR] 38%) and for recurrent patients 88% (CR 38%, PR 50%). Predominant toxicities were nausea, vomiting, myelosuppression, mucositis, and renal impairment. The median survival of the previously untreated patients, based on response to chemotherapy, was as follows: CR 21+ months (range, 10+ to 81 months), PR 13.5 months (range, 2 to 21 months), and no response (NR) 3 months (range, 1 to 7 months). The median survival of patients with recurrent disease was as follows: CR 16 months, PR 13.5 months, and NR 5 months. We conclude that patients with paranasal cancers are responsive to CDDP-containing combinations. The role of adjuvant chemotherapy in previously untreated, locally advanced patients needs to be demonstrated by future randomized trials.     

Multicenter phase II trial of combination chemotherapy with weekly paclitaxel and 5-fluorouracil for the treatment of advanced or recurrent gastric carcinoma

The aim of this study was to investigate the efficacy and safety of combination chemotherapy with weekly paclitaxel and 5-fluorouracil (5-FU) as first-line treatment in patients with advanced or recurrent gastric carcinoma. A total of 65 patients were treated with the following regimen, administered every 28 days; 5-FU 600 mg/m2 by 24-hour continuous infusion from days 1 through 5, and weekly paclitaxel 80 mg/m2 by 3-hour intravenous infusion on days 8, 14, and 21. A total of 272 cycles were conducted with a median of 4 (2-13) cycles per case. Out of 57 patients with measurable disease by RECIST criteria, there were 2 complete responses (3.5%), 20 partial responses (35.1%) and 25 cases with stable disease (43.9%). The overall response rate was 38.6% (95%CI: 26.0-51.2%). The median survival time and 1-year survival rates were 329 days and 47.4%, respectively. Both hematologic and non-hematologic toxicities were well tolerated.     

Phase II evaluation of paclitaxel in combination with carboplatin in advanced head and neck carcinoma.

BACKGROUND: Two-thirds of patients with squamous cell carcinomas of the head and neck (SCCHN) at diagnosis have advanced disease with projected 5-year survival rates of 30%. In those patients with distant metastatic or previously treated recurrent disease, response rate to the standard regimen of cisplatin and 5-fluorouracil is approximately 30%. The authors investigated the use of paclitaxel and carboplatin in a limited Phase II study in recurrent or metastatic SCCHN to evaluate tumor response, time to progression, survival, and toxicities of this regimen. METHODS: Patients with recurrent or metastatic SCCHN not amenable to further surgical or radiation therapy were treated with 200 mg/m(2) by 3-hour infusion of paclitaxel followed by carboplatin at an area under the concentration time curve of 6 mg/mL/minute via a 20-30-minute infusion every 3 weeks. RESULTS: Thirty-seven patients were enrolled. Ninety-five percent of patients had received prior surgery and postoperative radiotherapy. The overall response rate was 27% (95% confidence interval, 13-41%) with 1 complete and 9 PRs. Median survival of all patients was 4.9 months, and 1-year survival rate was 16%. There was a 43% response rate and 15.7-month median survival rate in patients with only distant metastatic disease and 38% response rate and a 4.5-month median survival in patients with locoregional and metastatic disease. The response rate for patients with only locoregional recurrence was 7% with a median survival of 4.8 months. Grade 3-4 myelotoxicity occurred in 24% of cycles administered. There were two treatment-related deaths due to neutropenic fever and one additional death on study may have been caused by treatment-induced thrombocytopenia. CONCLUSIONS: The combination of paclitaxel and carboplatin is significantly myelotoxic and ineffective in patients with previously treated locoregionally recurrent SCCHN, whereas it deserves further evaluation in those patients with distant metastatic disease alone. In those patients with locoregional disease, other more innovative treatments are needed.     

Phase II trial of paclitaxel and cisplatin in metastatic and recurrent carcinoma of the uterine cervix.

PURPOSE: Both paclitaxel and cisplatin have moderate activity in patients with metastatic or recurrent cancer of the cervix, and the combination of these two agents has shown activity and possible synergism in a variety of solid tumors. We administered this combination to patients with metastatic or recurrent cervical cancer to evaluate its activity. PATIENTS AND METHODS: Thirty-four consecutive patients were treated on an outpatient basis with paclitaxel 175 mg/m2 administered intravenously over a 3-hour period followed by cisplatin 75 mg/m2 administered intravenously with granulocyte colony-stimulating factor support. The chemotherapy was administered every 3 weeks for a maximum of six courses. RESULTS: Sixteen patients (47%; 95% confidence interval, 30% to 65%) achieved an objective response, including five complete responses and 11 partial responses. Responses occurred in 28% of patients with disease within the radiation field only and in 57% of patients with disease involving other sites. The median duration of response was 5.5 months, and the median times to progression and survival for all patients were 5 and 9 months, respectively. Grade 3 or 4 toxicities included anemia in 18% of patients and granulocytopenia in 15% of patients. Fifty-three percent of patients developed some degree of neurotoxicity; 21% of cases were grade 2 or worse. CONCLUSION: The combination of paclitaxel with cisplatin seems relatively well tolerated and moderately active in patients with metastatic or recurrent cervical cancer. The significant incidence of neurotoxicity is of concern, and alternative methods of administration of the two agents could be evaluated. Then, further study of this combination, alone or with the addition of other active agents, is warranted.     

Rapidly alternating radiotherapy and high dose cisplatin chemotherapy in stage IIIB non-small cell lung cancer: results of a phase I/II study.

Alternating radiotherapy and chemotherapy increases tumor cure rates in some animal models with reduced normal tissue damage compared to sequential use of these modalities. To test this concept in non-small cell lung cancer, 23 patients with predominantly Stage IIIB disease were treated on a Northern California Oncology Group pilot study of alternating radiotherapy and high dose cisplatin. Radiotherapy consisted of 6000 cGy delivered in three separate 10-day courses of 200 cGy/fraction/day during weeks 1 and 2, 5 and 6, and 9 and 10. High dose cisplatin, 100 mg/m2 in 3% saline, was administered on weeks 3 and 4, 7 and 8, 11 and 12, and 15 and 16. The response rate in 22 eligible patients is 73% (16/22) with four complete responses and 12 partial responses. Feasibility of this approach is demonstrated by 20/22 patients completing radiotherapy and a median of 2.5 courses of chemotherapy administered. Median survival time is 14.2 months (range 2-40+ months). One- and 2-year survival rates are 64% (14/22) and 41% (9/22), respectively. Hematologic, renal, and radiation-related toxicities were significant but manageable. We conclude that rapid alternation of radiotherapy and a high dose intensity cisplatin regimen is feasible in Stage IIIB non-small cell lung cancer, with a high response rate and acceptable toxicity. The long-term impact on local control and survival remains unclear, although preliminary survival data are encouraging in this poor prognosis population. Further studies of this concept are warranted.     

Phase II study with the combination etoposide, doxorubicin, and cisplatin in advanced measurable gastric cancer

In this phase II multicenter trial, 67 evaluable patients with advanced measurable gastric carcinoma were treated with a combination of etoposide, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and cisplatin (EAP). The overall response rate was 64%, including 21% complete responses (CRs). In 55 patients with metastatic disease, 31 responses (51%) including eight CRs (15%) were achieved. Responses were seen in all metastatic sites, but the response rate was lower in patients with peritoneal carcinomatosis. In 12 patients with locoregional disease, six CRs and six partial responses (PRs) were observed. Eight CRs (three and five in patients with metastatic and locoregional disease, respectively) were pathologically confirmed. The overall median response duration was 7 months; it was 16 months for patients achieving CR (22 months for pathologically confirmed CR [pCR]), and 6 months for PR. The median survival time for all patients was 9 months, for the patients who achieved CR 17 months, for pCR 23 months, and for PR 9.5 months. Median survival time for all patients with metastatic disease was 8 months, and for locoregional disease 12.5 months. Six patients (9%) (four local, two metastatic disease) were alive at 2 years, and four patients are alive and disease free at 35+ to 56+ months. Main toxicities were leukopenia and thrombocytopenia, with 64% of patients developing grade 3 to 4 myelosuppression and 12% severe infections. Nonhematologic toxicities of World Health Organization (WHO) grade 4 were not observed.     

A phase II evaluation of a 3-hour infusion of paclitaxel, cisplatin, and 5-fluorouracil in patients with advanced or recurrent squamous cell carcinoma of the head and neck: Southwest Oncology Group study 0007

BACKGROUND: Previous data from an institutional pilot study in patients with advanced or recurrent squamous cell carcinoma of the head and neck (SCCHN) who received treated a combined chemotherapy regimen of paclitaxel, cisplatin, and 5-fluorouracil indicated an overall response rate of 60% and a median survival of 6 months. To validate these results and to determine the feasibility of this combination, a Phase II study was conducted by the Southwest Oncology Group (SWOG S0007). METHODS: Patients with advanced or recurrent SCCHN were eligible if they had received 1 previous regimen of induction/adjuvant chemotherapy or no prior systemic therapy. Patients received treatment with paclitaxel (135 mg/m(2) on Day 1), followed by cisplatin (75 mg/m(2) on Day 1), and 5-fluorouracil (1000 mg/m(2)per day as a 96-hour continuous infusion on Days 1-4) every 21 days. RESULTS: Seventy-six patients received a combined total of 286 cycles of chemotherapy. Sixty-nine patients were evaluable for response. There were 5 complete responses (7%) and 23 partial responses (33%) partial responses, for an overall response rate of 41%. The median progression-free survival was 4 months, and the median overall survival was 10 months. Six treatment-related deaths were documented, including deaths in 2 patients who had a Zubrod PS of 2. Grade 3 or 4 neutropenia (according to National Cancer Institute Common Toxicity Criteria [version 2.0]) was observed in 47% of patients. Other Grade 3 or 4 adverse events included mucositis (34% of patients), nausea (20% of patients), anemia (9% of patients), and neuropathy (8% of patients). CONCLUSIONS: The combination of paclitaxel, cisplatin, and 5-fluorouracil had efficacy similar to that of standard treatment regimens in patients with advanced or recurrent SCCHN but with increased toxicity.