Acute cerebrovascular toxicity after chemotherapy with carboplatin and cyclophosphamide for advanced ovarian carcinoma

A 57-year-old woman with advanced ovarian cancer suffered an acute vascular ischemic event after receiving chemotherapy with carboplatin and cyclophosphamide. She experienced transitory speech disorder, left hemiplegia, and left planotopokinesia. The cerebrovascular symptoms resolved approximately 6 h after their acute onset. We suggest that these symptoms were toxic but reversible side effects of the chemotherapy with these two agents. Received: February 6, 1998 / Accepted: June 18, 1998     

Multicenter phase II study of weekly paclitaxel plus cisplatin combination chemotherapy in patients with advanced gastric cancer

Purpose Since a weekly administration of paclitaxel has demonstrated a sustained efficacy and more favorable toxicity profile than a 3-weekly administration for various solid tumors, the present study was conducted to evaluate the efficacy and safety of a combination regimen of weekly paclitaxel plus cisplatin in patients with advanced gastric cancer. Patients and methods Patients with previously untreated metastatic or recurrent, measurable gastric cancer received intravenous paclitaxel 100 mg/m² plus cisplatin 35 mg/m² on days 1 and 8 based on a 3-week cycle. Results Fifty-two patients were enrolled in the current study. Two complete responses and 17 partial responses were confirmed, giving an overall response rate of 36.5%. At a median follow-up of 8.5 months, the median time to progression and median overall survival was 6.0 and 10.8 months, respectively. Grade 3 neutropenia occurred in ten patients, while no grade 4 neutropenia or febrile neutropenia was observed. The most common non-hematologic toxicity was nausea (grade 1/2, 56.9%). There were no treatment-related deaths. Conclusion A weekly paclitaxel and cisplatin combination was found to be well-tolerated and effective in patients with advanced gastric cancer. Accordingly, this regimen can be regarded as an important first-line treatment option for advanced gastric cancer.     

Hyperthermic intraperitoneal chemotherapy with cisplatin and paclitaxel in advanced ovarian cancer: a multicenter prospective observational study

Objective

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been recently reported with favorable oncological outcomes as treatment of advanced epithelial ovarian cancer (EOC). The aim of this study was to demonstrate the feasibility of CRS+HIPEC with cisplatin and paclitaxel for the treatment of advanced EOC.

Methods

This is a prospective observational study of 54 patients, from April 2007 to October 2013, with primary or recurrent peritoneal carcinomatosis due to EOC. The mean age was 54.51±9.34. Thirty patients (59%) had primary EOC, and 24 patients (41%) had recurrent disease.

Results

Mean peritoneal cancer index was 10.11 (range, 0 to 28), complete cytoreduction (CC0) was achieved for 47 patients (87%), CC1 for seven patients (13%). Patients with suboptimal cytoreduction (CC2 and CC3) were not included in the study. The mean stay in intensive care unit was 4.73±5.51 days and the mean hospitalization time was 24.0±10.03 days. We did not observe any intraoperative death. Seven patients (13%) required additional operations. Three patients (5.6%) died within 30 days from the procedure. Severe complications were seen in 19 patients (35.2%). During the follow-up period, disease recurred in 33 patients (61.1%); the median disease-free survival time was 12.46 months and the median overall survival time was 32.91 months.

Conclusion

CRS+HIPEC with cisplatin and paclitaxel for advanced EOC is feasible with acceptable morbidity and mortality. Additional follow-up and further studies are needed to determine the effects of HIPEC on long term survival.     

Tau protein as a potential predictive marker in epithelial ovarian cancer patients treated with paclitaxel/platinum first-line chemotherapy

Background

The aim of the study was to evaluate predictive and prognostic significance of microtubule-associated protein Tau in epithelial ovarian cancer (EOC) patients treated with paclitaxel and platinum-based chemotherapy.

Methods

74 patients with EOC (stage I-IV) who underwent cytoreductive surgery followed by standard paclitaxel/platinum chemotherapy were included in the retrospective analysis. Their formalin-fixed, paraffin-embedded tissue specimens were immunohistochemically stained for Tau protein, using semi-quantitative DAKO test. Tau expression was acknowledged as negative (0 and 1+) or positive (2+ and 3+). The correlation between Tau expression, progression free survival (PFS) and overall survival (OS) was evaluated. Statistical analysis included Kaplan-Meyer estimator, long rank test, Mann Whitney test and Cox proportional hazards model.

Results

25.7% (19/74) and 74.3% (55/74) of the patients were classified as Tau-negative and Tau-positive, respectively. Median PFS was 28.7 months for Tau-negative group and 15.9 months for Tau-positive group (p = 0.0355). In the univariate analysis 3-year OS in Tau-negative and Tau-positive groups was 80.2% and 52.4%, respectively (p = 0.0198). Low expression of protein Tau was associated with better OS, whereas an advanced stage at diagnosis, suboptimal surgery, serous histological type and resistance to first line chemotherapy were each correlated with worse OS (p <0,05). In multivariate analysis only resistance to first line chemotherapy remained significant (HR 22.59; 95% CI, 8.71-58.55; p <0.0001).

Conclusions

Negative tau protein seems to be both good prognostic factor and a predictor of response to paclitaxel/platinum-based chemotherapy in EOC patients.     

A feasibility study of sequential paclitaxel and S-1 (PTX/S-1) chemotherapy as postoperative adjuvant chemotherapy for advanced gastric cancer

Background The most frequent recurrence pattern of advanced gastric cancer is peritoneal dissemination. We investigated the safety of and compliance with sequential chemotherapy consisting of paclitaxel and S-1, both of which are effective in the treatment of peritoneal dissemination. Methods The patients in the study all had histologically proven gastric cancer, classified according to the TNM and the Japanese criteria for gastric cancer as T3–4, N0–2, P0, H0 M0, and CY0–1. In all patients, standard gastrectomy of more than a D2 dissection was performed. A dose of 80 mg/m² of paclitaxel was administered for three courses. One course comprised weekly administration for 3 weeks, followed by a 1-week rest, except for the first course (following S-1 administration at 80 mg/m² body surface area), in which paclitaxel was administered for only 2 weeks, followed by a 1-week rest. S-1 was administered from day 78 for four courses, with one course comprising 2 weeks' administration followed by a 1-week rest. Fifty patients received paclitaxel chemotherapy. The median age was 62.5 years overall; among the 34 male patients it was 65.5 years, and among the female patients it was 48.0 years. Results The patient compliance rate was 84%. There were no cases of grade 4 hematological toxicity during either paclitaxel or S-1 treatment. With respect to nonhematological toxicities, there was one case of grade 3 neuropathy during the course of paclitaxel treatment and one case of grade 3 diarrhea during the course of S-1 treatment. These patients recovered and completed the scheduled treatment regimen. Conclusion Sequential chemotherapy of paclitaxel and S-1 as postoperative adjuvant chemotherapy for advanced gastric cancer is feasible.     

Intraperitoneal chemotherapy in patients with advanced ovarian cancer: the con view

OBJECTIVES: In this paper we wish to present the reasons why i.p. chemotherapy cannot be accepted as standard of care for first-line systemic treatment of advanced ovarian carcinoma. METHODS: The recent literature on i.p. chemotherapy is critically reviewed. All possible arguments against i.p. chemotherapy are reviewed. CONCLUSIONS: Intraperitoneal chemotherapy is associated with a higher toxicity rate than i.v. chemotherapy. For this reason, none of the regimens investigated in the three Gynecologic Oncology Group (GOG) studies can be used as standard treatment outside clinical protocols. The trials on i.p. chemotherapy have suggested a survival difference. However, in the two most recent trials, i.p. chemotherapy or not was not the only research question because different schedules and dosages were used. In addition, the significance of the most recent GOG 172 study was only weak (p = .03), and the result was nonsignificant for progression-free survival. Intraperitoneal chemotherapy should be used only in the context of properly designed clinical trials. These trials must either assess i.p. therapy in comparison with the standard treatment or address the issue of route of administration for equivalent dosages and schedules of the same drugs, and not a mosaic of these questions. In addition, these trials should investigate i.p. regimens that are less toxic than the regimens used in the three GOG trials, and which can be combined with molecular targeted therapies.     

GP方案与TP方案一线治疗晚期非小细胞肺癌的临床观察

目的：探讨GP方案和TP方案对初治的晚期非小细胞肺癌（NSCLC）的疗效和毒性。方法：72例晚期NSCLC（ⅢB期50例,Ⅳ期22例）随机分成GP组和TP组,人组的每例患者接受至少2个周期以上的GP或TP同样方案的化疗,比较两组不同化疗方案的近期疗效和毒副反应,以及1、2年的生存率。结果：GP和TP两组近期疗效的有效率分别为44．4％和47．2％,两组中位生存期分别为8．7月和8．5月,1年生存率分别为16．6％和19．4％,2年生存率分别为8．3％和11．1％。两组资料统计学处理均无显著性差异。毒副反应方面,GP组以血小板降低为主,TP组以白细胞降低为主,均在可耐受的范围内。结论：GP和TP两种化疗方案对晚期NSCLC均有较好的临床疗效,化疗毒副反应虽有所不同,但均可耐受。因此GP和TP两种化疗方案均可作为晚期NSCLC的一线治疗方案。     

中晚期宫颈癌术前介入治疗的临床研究

目的探讨术前应用髂内动脉灌注化疗及血管栓塞疗法的介入治疗,提高中晚期宫颈癌手术切除率的可行性。方法治疗组22例,给予顺铂和氟尿嘧啶髂内动脉介入并血管栓塞治疗,并于介入后第2天静脉给予紫杉醇240mg。对照组23例,静脉给予紫杉醇＋顺铂＋氟尿嘧啶化疗。结果治疗组总有效率为81．8％,其中50％经双路化疗后手术切除病灶。对照组总有效率34．8％,其中有17．3％的患者手术切除。治疗组疗效优于对照组（P〈0．01）。结论中晚期宫颈癌术前的双路化疗,提高了手术切除率,使患者的生存率及生存质量均有明显提高。     

Paclitaxel-cisplatin combination in advanced ovarian cancer: a phase II study

Background. To date there have been four large randomized studies in Western countries examining the role of combining cisplatin and paclitaxel as first-line treatment for ovarian cancer. A phase II study of paclitaxel and cisplatin in Japanese patients with advanced ovarian cancer was performed to determine the objective response rate and toxicity of this regimen. Methods. Previously untreated patients with stage III or IV ovarian cancer and a good performance status were eligible. Treatment consisted of paclitaxel 180 mg/m² administered as a 3-h intravenous (i.v.) infusion followed by cisplatin 60 mg/m² i.v. Treatment was repeated every 3 weeks for at least four cycles. Granulocyte colony-stimulating factor (G-CSF) was not routinely used. Results. Among 26 eligible patients, there were 4 complete and 17 partial responses, for an overall response rate of 80.8% (95% confidence interval [CI], 60.6% to 93.4%). One hundred and twenty-nine treatment cycles were administered to the 26 patients. Grade 4 neutropenia was observed in 64 treatment cycles (50%) and in 23 patients (88%). Thrombocytopenia was less common. The most common nonhematologic toxicities included neurotoxicity, fatigue, arthralgia/myalgia, and nausea/emesis. Conclusion. Paclitaxel plus cisplatin is a highly active regimen in patients with advanced ovarian cancer. The toxicities of this regimen are well tolerated. Received: September 1, 1999 / Accepted: January 11, 2000     

Evolving concepts in the management of drug resistant ovarian cancer: Dose dense chemotherapy and the reversal of clinical platinum resistance

Despite the initially high response rate to standard front-line debulking surgery followed by platinum-based chemotherapy, the relapse rate in ovarian cancer is high and many patients will recur within 6 months of completing platinum based treatment. These patients may still require further chemotherapy despite being considered “platinum resistant”. In this setting, response rates to conventionally scheduled second line platinum and non-platinum agents is low, ranging between 5% and 15%. There is an emerging body of evidence that in this scenario, chemotherapeutic activity can be enhanced using unconventionally scheduled “dose-dense” platinum and non-platinum based regimens with improved response rates of up to 65%. Randomised studies to evaluate the impact of this approach on survival in recurrent, platinum resistant disease are urgently required to confirm the promising phase II findings if there is to be a change in the standard of care of patients with platinum resistant disease. In this review we discuss the evolving strategies to overcome resistance in patients with platinum resistant ovarian cancer with a particular focus on alterations in dose schedule as a means of reversing platinum resistance.     

The prognostic impact of duration of anemia during chemotherapy in advanced epithelial ovarian cancer

Objective.

To propose a measure of anemia to be used as a prognostic factor for progression-free survival and overall survival in advanced epithelial ovarian cancer patients.

Patients and Methods.

Seventy-six patients with International Federation of Gynecology and Obstetrics stage III and stage IV epithelial ovarian cancer who had received at least six courses of platinum- and taxane-based systemic chemotherapy and achieved clinical or pathologic complete response were included. A novel prognostic factor based on the duration of anemia was proposed and the impact of anemia on progression-free and overall survival times was analyzed by a log-rank test and a Cox proportional hazards model.

Results.

We introduce a binary variable, Hb1020, that takes a value of 1 if the duration of a hemoglobin (Hb) level <10 g/dL is ≥20% of the total duration of chemotherapy. We propose Hb1020 as a potential prognostic factor for epithelial ovarian cancer. The 5-year progression-free survival rates were 48.4% in the Hb1020 = 0 group (duration of Hb <10 g/dL <20% of total duration) and 17.7% in the Hb1020 = 1 group (p = .026). The 5-year overall survival rates were 64.6% and 45.0%, respectively (p = .015).

Conclusions.

Hb1020, based on the duration of anemia, is a potential prognostic factor for epithelial ovarian cancer. Using Hb1020, we will be able to administer highly optimized treatment for anemia to improve patient survival. Further independent studies are needed to confirm its prognostic role.     

Pathologic chemotherapy response score in epithelial ovarian cancer: Surgical,genetic, and survival considerations

ObjectiveA pathologic chemotherapy response score (CRS) is used to grade ovarian cancer response to neoadjuvant chemotherapy (NACT). We evaluated the prognostic significance of the CRS in a single institution cohort.MethodsA retrospective review of all consecutive epithelial ovarian cancer patients undergoing interval debulking surgery (IDS) after NACT from 2016 to 2017 were included. Clinical, pathologic, surgical, outcomes, and genetic data were abstracted from medical records. CRS was assigned by pathology based on a section of omentum as follows: 1 = minimal response, 2 = moderate response, and 3 = near complete response.ResultsAmong the 50 subjects, 14 (28%) were classified as CRS1, 29 (58%) as CRS2, and 7 (14%) as CRS3. The majority of patients were diagnosed with high grade serous histology (94%). Most women in this cohort underwent either an optimal or complete cytoreduction to no gross residual disease (96%). Women in the CRS2 group were most likely to have a pathogenic variant (51.7%) while those in the CRS1 were least likely (7.1%). Most women recurred regardless of CRS. CRS was not associated with progression-free survival (log-rank p = 0.82) or overall survival (log-rank p = 0.30).ConclusionsThough previous data support the use of CRS as a prognostic indicator, we failed to show a correlation between CRS and survival in our continuous single institution cohort. The high rate of optimal debulking across all CRS groups in this study may mitigate the prognostic significance of the scoring system. Nevertheless, tumors that respond poorly to traditional chemotherapy should remain of avid interest for potential novel therapies.     

Induction of p53 and drug resistance following treatment with cisplatin or paclitaxel in ovarian cancer cell lines

Treatment failures result from resistance to chemotherapy in ovarian cancer. The effect of cisplatin and paclitaxel treatments on chemosensitivity was studied in ovarian cancer cells developed from a patient with stage IIIC disease. Cells (UL-3A, UL-3B) that recovered from cisplatin (Cis) and paclitaxel (Tax) treatments showed higher levels of p53, mdr-1 and chemoresistance than untreated controls. EC50 values of Cis and Tax for UL-3A clones were 7.2-34.6, average 20.9 microg/ml, while UL-3B clones ranged from 11.8-252.0 microg/ml, with a mean value of 73.2 microg/ml for Cis, and 260.0-4400.0 nM (mean 2555.0 nM) for Tax. Selection pressures during treatment may contribute to drug resistance.     

A phase I combination chemotherapy study of biweekly paclitaxel and S-1 administration in patients with advanced gastric cancer

The aim of the current study was to determine the maximum tolerated dose (MTD) and the dose limiting toxicity (DLT) of a combination of paclitaxel and S-1 in patients with advanced gastric cancer. Fifteen patients were enrolled. The dose for S-1 was set at 80 mg/m²/day (days 1–14), while the dose for paclitaxel increased by 10 mg/m² for every three patients, with a starting dose of 100 mg/m² and was given biweekly on day 1 and 15. There was no severe toxicity (grade 4) recorded in patients receiving up to 120 mg/m² of paclitaxel. Leukopenia/neutrophilia with grade 1 to 3 occurred in six patients up to level 3. At 130 mg/m² of paclitaxel, grade 4 leukocytopenia and neutropenia events and grade 3 diarrhea developed in one out of three patients. One patient in another group of three patients that were enrolled at level 3, developed grade 4 granulocytopenia with fever (a body temperature higher than 38°C) and grade 3 leukocytopenia. Eight patients, out of a total of 15, showed a partial response, resulting in an objective response rate of 53%. Five patients received gastrectomy. Median survival time was 428 days and the 1 year survival rate was 53%. Biweekly paclitaxel/S-1 combination chemotherapy could be safely used for the treatment of advanced gastric cancer. The recommended doses for a phase II study with paclitaxel and S-1 are 120 mg/m² and 80 mg/m², respectively.     

血清miR-143水平与晚期胃癌含紫杉醇化疗方案敏感性的关系分析

目的 探讨晚期胃癌血清microRNA-143（miR-143）水平与含紫杉醇方案化疗敏感性的关系。方法 收集本院2012年1月至2016年7月收治的82例晚期胃癌患者,均接受含紫杉醇联合铂类或氟尿嘧啶类药物,收集其化疗前的血清标本并采用实时荧光定量PCR（QPCR）法检测其miR-143水平,与同期76例健康体检者的miR-143水平进行比较;分析不同miR-143水平与临床病理特征的关系,采用RECIST1.1版标准评价近期疗效并比较不同miR-143水平与化疗敏感性的关系,根据随访资料比较不同miR-143水平的中位无进展生存期（PFS）和总生存期（OS）。结果 QPCR检测发现82例胃癌患者的miR-143水平为0.215±0.021,低于76例健康体检者的1.099±0.057,差异有统计学意义（P<0.05）。血清miR-143水平与性别、年龄、ECOG评分、肿瘤部位及病理类型均无关,但与TNM分期和分化程度有关,差异有统计学意义（P<0.05）。化疗敏感（CR+PR）31例患者的血清miR-143水平为0.341±0.040,高于化疗抵抗（SD+PD）51例患者的0.138±0.015,差异有统计学意义（P<0.05）。以miR-143水平的中位值（0.177）将患者分为高表达组（>0.177）和低表达组（≤0.177）,高表达组的总有效率、中位PFS和OS分别为48.8%、8.5个月和12.2个月,优于低表达组的31.7%、7.3个月和9.4个月,差异有统计学意义（P<0.05）。结论 晚期胃癌血清miR-143水平低于正常值,且与含紫杉醇方案化疗敏感性及预后均有关,其中miR-143高表达者的敏感性较高且预后较好,在胃癌诊断及预后评估上有一定价值。     

Lack of influence of glutathione S-transferase gene deletions in sporadic breast cancer in Pakistan

Glutathione S-transferases constitute the phase II detoxification enzymes involved in the metabolism and detoxification of a wide range of potential environmental carcinogens. GSTM1 and GSTT1 are polymorphic and their deletions have been found to be associated with breast cancer risk in some of the world populations. The current study was aimed at evaluation of GSTM1 and GSTT1 gene deletions in 150 unrelated breast cancer patients and 150 healthy controls from Pakistani population. Multiplex PCR assay along with CYP1A1 exon 7 as an internal control was used. Our sampled patients and controls had a mean age of 48 (+11.8) and 45 (+7.9) years respectively. The analysis suggested that only 2% breast cancer patient and 8% controls had homozygous GSTM1 gene deletions (OR 0.23, 95% CI 0.06-0.85). A total of 8.7% patients and 18.6% controls had homozygous GSTT1 deletion (OR 0.41, 95% CI 0.25-0.83). The statistical analysis suggest that a non significant number (P>0.05) of individuals compared to controls have GSTM1 and GSTT1 gene deletions. Deletion in both genes was not observed in any of the patients or controls. The present case control study suggests no association of GSTM1 and GSTT1 gene deletions with sporadic form of breast cancer in Pakistani population.     

Synergistic effects of the sesquiterpene lactone,EPD, with cisplatin and paclitaxel in ovarian cancer cells

Background

Ovarian cancer remains still the leading cause of death of gynecological malignancy, in spite of first-line chemotherapy with cisplatin and paclitaxel. Although initial response is favorably, relapses are common and prognosis for women with advanced disease stays poor. Therefore efficacious approaches are needed.

Methods

Previously, an anti-cancer agent, EPD exhibited potent cytotoxic effects towards ovarian cancer and not towards normal cells. Cell viability and cell cycle analysis studies were performed with EPD, in combination with cisplatin and/or paclitaxel, using the ovarian carcinoma cell lines: SK-OV-3, OVCAR-3, JC, JC-pl and normal fibroblasts. Cell viability was measured using Presto Blue and cell cycle analysis using a flow cytometer. Apoptosis was measured in JC and JC-pl , using the caspase 3 assay kit.

Results

In JC-pl, SK-OV-3 and JC, synergistic interactions between either EPD and cisplatin or EPD and paclitaxel were observed. For the first time the effects of EPD on the cell cycle of ovarian cancer cells and normal cells was studied. EPD and combinations of EPD with cisplatin and/ or paclitaxel showed cell cycle arrest in the G₂/M phase. The combination of EPD and cisplatin showed a significant synergistic effect in cell line JC-pl, while EPD with paclitaxel showed synergistic interaction in JC. Additionally, synergistic drug combinations showed increased apoptosis.

Conclusions

Our results showed a synergistic effect of EPD and cisplatin in an ovarian drug resistant cell line as well as a synergistic effect of EPD and paclitaxel in two other ovarian cell lines. These results might enhance clinical efficacy, compared to the existing regimen of paclitaxel and cisplatin.

Electronic supplementary material

The online version of this article (doi:10.1186/s13046-015-0157-2) contains supplementary material, which is available to authorized users.     

Successful treatment of advanced gastric cancer by surgical resection following combination chemotherapy with oral S-1 and biweekly paclitaxel

We report on the successful treatment of advanced gastric cancer by surgical resection following neoadjuvant chemotherapy. A 67-year-old man was referred to our hospital with a diagnosis of pancreatic cancer. Meticulous examination, however, revealed the presence of gastric cancer with ascites and large lymph node metastasis adjacent to the pancreas. We selected combination chemotherapy with oral S-1 and biweekly paclitaxel. After two courses, both the primary tumor and metastatic lymph nodes were greatly reduced, and the ascites had disappeared. Using laparoscopy, there was no evidence of peritoneal metastases, and the cytological examination was negative. The patient underwent distal gastrectomy with D2 lymph node dissection. Histological examination revealed that the cancer cells were still present in part, but no lymph node metastases were found. The tumor was pathologically diagnosed as pT2, pN0, P0, M0, CY0, and p-stage II. The patient is healthy over 4 years after surgery without recurrence.     

Outpatient chemotherapy for recurrent and/or advanced squamous cell carcinoma of the head and neck

Background. The efficacy of the treatment of cancer has been traditionally judged by outcome measures such as disease-free survival, overall survival, and tumor response rate. Our goal of salvage and/or adjuvant chemotherapy is to improve not only the survival period but also the quality of life (QOL). The conventional regimens containing cisplatin (CDDP) require hospitalization of patients, which has been responsible for disappointingly low QOL. Thus, we developed a new outpatient regimen that has same magnitude of activity and less toxicity compared with conventional CDDP-containing regimens. Methods. Sixteen patients with recurrent or advanced head and neck cancer were treated by the outpatient setting Long-CF regimen. The Long-CF regimen consisted of cisplatin (CDDP) (CDDP, 5 mg/m²/2 h infusion on days 1–5, 8–12, 15–19, 22–26) and 5-fluorouracil (5-FU) [oral administration of tegaful-uracil (UFT-E), 400 mg/body on days 1–28]. Results. Among 16 patients entered in this trial, 1 patient was disqualified from analysis for reasons of protocol violation. Of 15 patients evaluable for response, 2 complete responses (13%) and 4 partial responses (27%) were achieved, with an overall response rate of 40%. Myelosuppression was the major side effect. Leukopenia and anemia (13% greater than WHO grade III) were dose-limiting toxicities. Other adverse reactions including mucositis were all mild and transient. Conclusion. As this regimen is given in an outpatient setting, we concluded that this regimen produced a beneficial effect in patients with recurrent and/or advanced head and neck cancer. Moreover, the toxicity of this regimen was limited; thus, attempts to increase the complete response rate by dose escalation or intensive scheduling appear warranted. Received: May 18, 1998 / Accepted: May 27, 1999