Concurrent Chemoradiotherapy for Salvage in Relapsed Squamous Cell Head and Neck Cancer

The results in 9 patients with unresectable recurrent squamous cell cancer of the head and neck who were treated with aggressive concurrent chemoradiotherapy are reported. Treatment consisted of one or two courses of chemotherapy with 5-fluorouracil 1000 mg/m²/day and cisplatin 20 mg/m²/day, both given as 4-day continuous intravenous infusions, concurrent with radiation therapy. Salvage radiation doses between 30 and 70 Gy were administered. Seven patients had previously undergone an attempt at curative surgery, and 7 had been treated with radiation doses between 52 and 72 Gy. The recurrent disease was locally confined in 3, locoregional in 5, and locore-gional with metastases in 1 of the 9 patients. Treatment toxicity was significant and included mucositis, nausea/vomiting, and granulocytopenia, but there were no toxic deaths. Complete tumor clearance was possible in 6 of these 9 patients, and 5 patients remain disease-free at 41+, 43+, 45+, 47+, and 50+ months. Of these 5 patients, 4 had previously been treated with both surgery and radiation, while 1 had only undergone surgery. We conclude that aggressive chemotherapy and concurrent (re)irradiation can be given to patients with unresectable, recurrent, squamous cell cancer of the head and neck. Treatment is tolerable, and disease-free long-term survival is possible. Careful patient selection, however, is required.     

Platinol (CDDP) and Continuous Intravenous Infusion 5-Fluorouracil in Refractory Stage IV Breast Cancer: A Phase II Study

Twenty-four patients with refractory Stage IV breast cancer were teated with platinol (100 mg/m² i.v. Day 1) and 5-fluorouracil (1000 mg/m² as a continuous infusion over 24 h daily for 5 days). Objective responses occurred in 12 of 24patients (50%). The median duration of response was 4.9 months. Platinol and 5-fluorouracil in combination are active agents in patients with refractory breast cancer, and clinical trials are warranted in previously untreated patients.     

Combined MTX.5-FU.CDGP for the treatment of head and neck cancer

Combination chemotherapy including 5-fluorouracil (5-FU) and nedaplatin (CDGP) with methotrexate (MTX) and leucovorin (LV) was administered for modulation in patients with head and neck cancer. We treated 19 patients with MTX.5-FU.CDGP consisting of 150 mg/body of MTX on day 1 followed by a 3-day continuous infusion of 5-FU at 3,500 mg/m2 and 17 injections of LV at 15 mg and infusion of CDGP at 100 mg/m2. Six patients had recurrent head and neck cancer, and 13 had newly diagnosed disease. Eleven of the new patients were concurrently treated with radiation therapy. Treatment-associated toxicity was significant, including mucositis and myelosuppression, but acceptable. Sixteen patients were eligible for evaluation of response. The overall complete response rate was 75.0% (12/16). Patients treated with radiotherapy had a 90.0% (9/10) overall complete response rate.     

Induction Chemotherapy (Cisplatin + 5-Fluorouracil) and Radiotherapy in Advanced Squamous Cell Carcinoma of the Head and Neck

A phase 11 study was made of 58 consecutive patients with previously untreated locally advanced squamous cell carcinomas of the head and neck. The induction chemotherapy consisted of 3 courses of cisplatin (100mg/m²) and a subsequent 120-h infusion of 5-fluorouracil (1 000 mg/m²/24 h) repeated every 3 weeks. It was followed by radiotherapy to a median target dose of 66 Gy and surgery for residual tumour. A total of 91 per cent received all 3 courses of chemotherapy, which was well tolerated. Complete response (CR) was obtained in 20 patients (35%) after chemotherapy and in 40 patients (69%) after subsequent radiotherapy. The median observation time was 28 months (range 15-57). The actuarial survival at 2 years for complete responders to chemotherapy was 83 per cent, implying a prolonged survival (p = 0.002) compared to those with less than CR. Complete responders after chemotherapy had also a significantly longer recurrence-free survival, though 19 out of 20 did not undergo surgery. Complete response after this induction therapy is thus an important prognostic predictor.     

表柔比星联合奥沙利铂及氟尿嘧啶的化疗方案提高局部进展期胃癌根治性手术机会的研究

背景与目的：转化性化疗能使肿瘤降期,提高胃癌根治性手术的切除率,改善胃癌患者的预后。本研究旨在探讨EOF方案是否可以提高局部晚期胃癌根治性手术切除率,同时评价转化性化疗的安全性和耐受性。方法：30例经病理证实为胃癌的患者,影像学评估为潜在可根治的局部进展期胃癌入组。采用EOF方案进行治疗,具体为奥沙利铂130 mg/m²,静脉注射(2 h),第1天;表柔比星50 mg/m²,静脉注射(2 h),第1天;氟尿嘧啶2 400 mg/m²,静脉注射(48 h),每3周重复1次,共行2~4个周期。化疗结束后进行临床疗效及不良反应的评估。结果：30例局部进展期胃癌患者接受了EOF方案的化疗,完全缓解(complete response,CR)为3.3%(1/30),部分缓解(partial response,PR)为26.7%(8/30),疾病稳定(stable disease,SD)为46.7%(14/30),疾病进展(progressive disease,PD)为23.3%(7/30),临床总有效率(CR+PR)为30%(9/30)。66.7%(20/30)的患者行手术切除,其中46.7%(14/30)获得根治性切除,20%(6/30)行姑息性手术。主要的化疗不良反应为白细胞减少53.3%(16/30),中性粒细胞减少53.3%(16/30),食欲减退43.3%(13/30),无化疗相关死亡。结论：EOF方案在局部进展期胃癌的治疗中是安全有效且耐受良好的方案。     

Evaluation of Two Consecutive Regimens in Advanced Gastric Cancer

Treatment of gastric cancer still presents a challenge in cancer chemotherapy. In our Institute, from January 1981 to November 1984, 45 patients were given 5-fluorouracil (5FU) 600 mg/m² Days 1, 8, 29, and 36; doxorubicin (A) 30 mg/m² Days 1 and 29; mitomycin-C 10 mg/m² Day 1 (FAM regimen) every 8 weeks. From December 1984 to October 1986, 26 patients were treated with 5FU 300 mg/m² on Days 1-5, A 40 mg/m² on Day 1, cisplatin (P) 100 mg/m² on Day 1 (FAP regimen) every 3 weeks. In the FAM group, 42 patients are evaluable for response; 5 (12%) partial remission (PR), 9 stable disease (SD), and 28 progressions (PRO) were observed. Median duration of response (MDR) was 21 weeks (range 13-45) and the median survival (MS) in the whole group was 27 weeks. In the FAP group, 23 patients are evaluable: 2 CR (9%), 11 PR (47%), 2 SD (9%), and 8 PRO (34%) were observed; CR duration was 24 and 107+ weeks, respectively, MDR of PR was 22 weeks (5-35). The MS of all patients was 16 weeks. Toxicity (WHO criteria) was mild in the FAM group and severe in the FAP group. In spite of a higher objective response rate, the short MS and the severe toxicity observed in the FAP group do not merit recommendation of this regimen in patients with gastric cancer; therefore neither FAM nor FAP appear to be an ideal standard therapy.     

Biweekly low-dose sequential gemcitabine, 5-fluorouracil, leucovorin, and cisplatin (GFP): a highly active novel therapy for metastatic adenocarcinoma of the exocrine pancreas

Phase II studies have suggested an improved response rate and acceptable toxicity profile associated with gemcitabine combinations compared to gemcitabine alone for treatment of metastatic adenocarcinoma of the pancreas. The GFP regimen (gemcitabine, 5-fluorouracil, leucovorin, and cisplatin) is based on laboratory evidence of disease-specific chemotherapy interaction.[8] This retrospective analysis examined the outcome of 49 consecutive patients with histologically confirmed metastatic pancreatic adenocarcinoma treated between July 1998 and September 2000. Day 1 treatment consisted of gemcitabine 500 mg/m² over 30 minutes and then leucovorin 300 mg bolus, 5-fluorouracil (5-FU) 400 mg/m² bolus, followed by infusional 5-FU 600 mg/m² over 8 hours. Day 2 consisted of leucovorin 300 mg bolus, 5-FU 400 mg/m² bolus, followed by cisplatin 50-75 mg/m² over 30 minutes and then infusional 5-FU 600 mg/m² over 8 hours. Treatment was administered every 2 weeks. Median patient age was 61.5 years, 74% were men, and 20 patients had refractory disease (11 patients had disease progression upon gemcitabine-based therapy). Grade 3-4 toxic effects (% patients) consisted of neutropenia (30%), thrombocytopenia (14%), anemia (8%), and neutropenic fever (2%). Grade 3-4 nonhematological toxicities (% patients) consisted of neuropathy (14%), ototoxicity (8%), nephrotoxicity (6%), nausea/vomiting (14%), and mucositis (10%). The majority of dose reductions were made for neuropathy or cytopenias. Filgrastim and erythropoietin were given as needed to promote dose intensity. Eight patients attained a partial response (PR) by RECIST criteria. Fourteen had stable disease (SD). Two patients attaining PR and two attaining SD had progressive disease with prior gemcitabine-based therapy. The median time to disease progression (TTP) from GFP start was 9 weeks. For all 49 patients, the median overall survival (OS) from GFP start was 10.6 months, 12-month survival was 46%, and 24-month survival was 30%. Notably, upon disease progression, 31 patients continued to receive the GFP regimen with irinotecan 80 mg/m² inserted on day 1 following gemcitabine, the G-FLIP regimen (gemcitabine, 5-fluorouracil, leucovorin, irinotecan, and cisplatin). Measured from G-FLIP initiation, the TTP for the 31 patients treated sequentially was 10 weeks, and for the 14 patients attaining SD or PR the TTP was 25 weeks. The median overall survival measured from GFP initiation was 11.8 months. The response rate, non-cross resistance, TTP, OS, and tolerability warrant prospective development of this novel combination. This experience also demonstrates that adding a single new drug such as irinotecan to the same first-line chemotherapy combination upon disease progression may be an important alternative for the treatment of relapsed/resistant cancer.     

Cisplatinum in Combination with 5-Fluorouracil and Citrovorum Factor in the Treatment of Advanced Colorectal Carcinoma

A phase 11 trial of citrovorum factor, 500 mg/m²/week, plus 5-fluorouracil, 400 mg/m²/week on day 1, and cisplatin, 20 mglm²lweek on day 2, was carried out in a group of 40 patients with metastatic colorectal carcinoma. A partial response with a mean duration of 8.4+ months was achieved in 24% of patients, a minimal response with a mean duration of 5.4 months was obtained in 6% of patients, and a stabilization of 6.2 months was achieved in 41%. Ten patients (29%) progressed. A 38% partial response rate was seen in patients with advanced rectal carcinoma, whereas no response was obtained in patients with colon cancer. Interestingly, 5 partial responses were seen in 12 patients pretreated with 5-fluorouracil. The overall survival was 9.8+ months. The mean survival of patients who achieved a partial response was 12.0+ months, whereas patients who progressed survived a mean of 6.6+ months. Patients with colon cancer had a mean survival of 8.1 + months, and those with rectal cancer survived a mean of 11A + months. This difference was not statistically significant. The treatment was generally very well tolerated, with patients showing mostly grade 1-2 gastrointestinal and Ior hematological toxicity.     

A phase II study of modified deGramont 5-fluorouracil, leucovorin, and oxaliplatin in previously treated patients with metastatic colorectal cancer

Purpose: To evaluate the toxicity and efficacy of a modified deGramont regimen of 5-fluorouracil (5-FU), leucovorin, and oxaliplatin in patients with advanced colorectal cancer who have progressed on at least one but not more than two prior chemotherapy regimens. Patients and Methods: Patients with stage 4 colorectal cancer were treated with oxaliplatin 85 mg/m² by a 2-hour intravenous infusion, followed by leucovorin 500 mg/m² by a 2-hour intravenous infusion, followed by 5-FU 400 mg/m² by bolus injection, followed by 5-FU 2.4 g/m² administered by a 46-hour continuous infusion. Cycles were administered every 2 weeks. Results: Seventy patients were treated and 68 patients had previously received irinotecan. Eleven percent of patients had a partial response, 33% of CEA-evaluable patients had a ≥50% drop in their CEA level. The median time to progression was 6.2 months, and the median overall survival was 8.7 months. Toxicity was mild to moderate, as 14% of patients experienced grade 3 or 4 neutropenia and 3% of patients experienced grade 3 neuropathy. Conclusion: The modified deGramont regimen of 5-FU, leucovorin, and oxaliplatin is tolerable and is associated with a modest degree of antitumor activity in patients who have progressed on both 5-FU and irinotecan.     

Combination Cisplatin and Carboplatin in Advanced Squamous Cell Carcinoma of the Head and Neck

Twenty-three patients with advanced squamous cell carcinoma of the head and neck who had received no prior chemotherapy were treated with carboplatin 350 mg/m² followed by cisplatin 50 mg/m² every 28 days. Twenty-one of 23 patients were evaluablefor response and toxicity. Eight patients (38%) achieved complete response (CR) or partial response (PR) with 2 CR and 6 PR. The overall median survival was 8.4 months (range 19 days-56% months). The major toxicity was hematological with grade III/IV granulocytopenia in 32% and grade III/IV thrombocytopenia in 32%. There was very little nonhematological toxicity and no nephrotoxicity. There were no therapy-related deaths. The combination carboplatin/cisplatin is tolerable in patients with squamous cell carcinoma of the head and neck, with objective responses in 38%; however, the response rate was not superior to single-agent carboplatin or cisplatin. Further studies with a higher dose of cisplatin should be considered.     

Chemoradiation therapy using radiotherapy, systemic chemotherapy with 5-fluorouracil and nedaplatin, and intra-arterial infusion using carboplatin for locally advanced head and neck cancer - Phase II study

To improve the treatment results for locally advanced head and neck cancer, chemoradiation therapy by radiotherapy, systemic chemotherapy with 5-fluorouracil (5FU) and nedaplatin (NDP), and intra-arterial therapy using carboplatin (CBDCA) was performed. Thirty-two patients were entered into the study between July 1997 and August 2002. According to the TNM staging (1997), 14 patients had stage III lesions, and 19 patients had stage IV (M0) lesions. Alternating chemoradiotherapy was performed by the following regimen. Initially, systemic chemotherapy was administered, followed by 4 weeks of radiotherapy (36 Gy/20 fractions; wide field irradiation) starting 2 days after chemotherapy, a second course of systemic chemotherapy 2 days after radiotherapy, and a second course of a reduced field radiotherapy (30 Gy/15 fractions) 2 days after chemotherapy. Arterial injection therapy was administered in the latter half of radiotherapy after the end of the second course of systemic chemotherapy. For systemic chemotherapy, 5FU at 3500 mg/m²/120 h was intravenously administered for 5 days (Days 1–5), and NDP at 120 mg/m²/6 h was administered on Day 6. An intra-arterial agent using CBDCA was continuously infused by a portable electrical pump for 4 (to 6) weeks. The total dose of CBDCA was AUC 6 as established by Calvert’s formula. The 5-year local control rate was 59%. The 5-year overall survival rate was 51%. There were no clinically significant adverse effects. Chemoradiation therapy by radiotherapy, systemic chemotherapy, and intra-arterial chemotherapy for locally advanced head and neck cancer may be useful for improving treatment results.     

A phase I study of eniluracil/5-FU in combination with radiation therapy for potentially resectable and/or unresectable cancer of the pancreas and distal biliary tract

Purpose: Eniluracil is an effective inactivator of dihydropyrimidine dehydrogenase (DPD). It allows for oral dosing of 5-fluorouracil (5-FU), which may potentially improve the antitumor activity of 5-FU when delivered concurrently with radiotherapy while avoiding the inconvenience and morbidity of continuous infusion (CI) 5-FU. We addressed the safety of oral eniluracil/5-FU combined with radiation therapy and determined the profile of dose-limiting toxicities and recommended Phase II dose (RPTD) in patients with pancreatic and hepatobiliary cancers. Methods and Materials: Patients with resectable or locally advanced pancreatic and biliary cancer received eniluracil (starting at 6.0 mg/m² q12h)/5-FU (starting at 0.6 mg/m² q12h). Eniluracil/5-FU were given concurrently with preoperative radiation to 4500 cGy followed by 540 cGy by reduced fields. Surgery was considered 4 weeks after completion of therapy. Results: Thirteen patients were enrolled. Chemoradiotherapy was completed in all patients. The MTD was not reached and, thus, the RPTD of eniluracil/5-FU was determined to be 10 mg/m² q12h/1 mg/m² q12h. Two patients with locally advanced disease had a 30-45 percent cross-sectional tumor reduction, one of which underwent margin-negative resection. Two of 5 patients with pancreatic cancer, and 1 of 3 patients with cholangiocarcinoma, with underwent exploratory surgery had margin-negative resections. One patient had a pathologic complete response (pCR). Patient 5-FU plasma exposure increased slightly from Day 8 to Day 31. Conclusion: Preoperative chemoradiation with oral eniluracil/5-FU is feasible, well tolerated, and potentially effective in the neoadjuvant setting. Further investigation of oral fluoropyrimidines as radiosensitizers for pancreaticobiliary malignancies is warranted.     

A Phase I Study of Escalating Interferon Alpha-2A Combined with 5-Fluorouracil and Leucovorin in Patients with Gastrointestinal Malignancies

On the basis of preclinical data showing synergy between 5-fluorouracil (5-FU), leucovorin (LV) and IFN-alpha-2a, a phase I study was carried out to determine the maximum tolerable dose (MTD) of IFN-alpha-2a with this combination in patients with gastrointestinal malignancies. The treatment consisted of 370 mg/m² 5-FU and 200 mg/m², LV on days 1 to 5, and IFN-alpha-2a on days 1 to 5 of the first week of chemotherapy and on days 1, 3, 5 of each subsequent week, on a 28-day cycle. Six patients with colorectal, 3 with pancreas, 2 with oesophagus, 2 with hepatocellular and one with gastric cancer were treated. At level III (5 × lo⁶ U/m²) all patients experienced grade 3 or 4 toxicity during the first 56 days of treatment and the MTD was declared level II. Grade 3 toxicity comprised of anorexia, mucositis, diarrhoea, and fatigue; in one instance, grade 4 neutropenia occurred. Ten patients were evaluable for response, one patient with an oesophageal cancer had a minor response and one patient with rectal cancer and liver metastases had a radiological complete response lasting 3 months. The recommended dose for this schedule in phase TI studies is 5-FU 370 mg/m², LV 200 mg/m², and IFN-alpha-2a 4 × 10⁶ U/m².     

Platinum-Based Chemotherapy Followed by Radiation Therapy of Locally Advanced Nasopharyngeal Cancer a Retrospective Analysis of 39 Cases

A retrospective analysis was performed of 39 patients with locally advanced nasopharyngeal cancer treated with combined chemotherapy and radiation therapy during the last five years, at our departments. There were 26 men and 13 women with median age 55 (24-75) years. Histology was squamous cell carcinoma in 6 patients and undifferentiated carcinoma in the remaining 33 patients. Induction chemotherapy consisted of either regimen A (cisplatin 100mg/m² day 1, 5-FU 1000mg/m² days 2-6 as continuous infusion, bleomycin 15 mg days 15 and 29 i.m., mitomycin 4mg/m² day 22 and hydroxyurea 1 000mg/m² daily days 23-27) or regimen B (carboplatin 300mg/m² day 1, 5-FU 1 000mg/m²days 1-5 as continous infusion and methotrexate 1.2g/m² day 14 with leucovorin rescue). After completion of induction chemotherapy 13 patients (33%) had complete remission (CR) and 19 (49%) partial remission (PR). The CR rate was increased after radiation therapy to 72%. Survival rates were 88% at 12 and 78% at 24 months. Median time to progression was 29.5 months. In conclusion, induction chemotherapy with a platinum-based regimen followed by radiation therapy achieved a high rate of local control. If the treatment also prolongs survival must, however, be studied by randomized trials.     

A Phase I—II Study of Cyclophosphamide, Epidoxorubicin, Levofolinic Acid/5-Fluorouracil and Recombinant Human Granulocyte Colony Stimulating Factor in Metastatic Breast Carcinoma

Thirty patients with measurable metastatic breast carcinoma were treated with a combination of cyclophosphamide 600 mg/m² on day 1, levofolinic acid 100 mg/m² plus 5-fluorouracil 375 mg/m² on days 1-3, and epidoxorubicin (EDXR) in three refracted doses on days 1-3 with G-CSF rescue for 10 days. In the phase I part of the study, groups of 3 patients received EDXR 20, 25, 30, 35, and 40 mg/m²/day until the dose limiting toxicity (DLT) was reached. At the dose of 40mg/m²/day prolonged grade 4 leukopenia, severe proctitis, and grade 3 diarrhea represented the DLT. All subsequent partients were treated at the maximal tolerated dose of EDXR (35 mg/m²/day). In the group of 18 patients treated at 35 mg/m²/day the overall response rate was 78%, with 22% CR and 56% PR. Four patients did not respond. Objective responses were seen at all tumor sites including bone and viscera, which usually are rather chemotherapy insensitive. Toxicity was generally acceptable. Although the response rate was quite high, the duration of objective tumor regression and patients' survival were not impressive. In conclusion, we do not recommend routine use of such an aggressive regimen for palliation of advanced breast cancer. Results of the present and similar studies may, however, be useful for planning of neoadjuvant or adjuvant trials with curative intent.     

Metastatic or Locally Advanced Colorectal Cancer Treated with 5-Fluorouracil and Low Dose Leucovorin

Eighty-one patients with metastatic or locally advanced colorectal cancer were treated at four oncological centers in Denmark with a regimen consisting of 5-fluorouracil 400 mg/m² and leucovorin 20 mg/m² for 5 consecutive days every 4 weeks. The response rate was 21% among all 81 patients (CR 3, PR 14). The median survival was 10 months regardless of measurability, sex and location of disease. Toxicity was mild, 6 (7%) patients were excluded from the study due to gastrointestinal side-effects and 15 (19%) patients had the 5-FU dose reduced due to side-effects. The results are comparable to those of other studies using different doses of leucovorin.     

Sequential administration of methotrexate, cisplatin, and 5-fluorouracil in multimodal therapy for locally advanced head and neck cancer

Thirty-eight previously untreated patients with locally advanced head and neck cancer received three cycles of induction chemotherapy with methotrexate (120 mg/m2) followed by cisplatin (100 mg/m2) and a 5-day continuous infusion of 5-fluorouracil (1,000 mg/m2 per day). The response rate in 34 evaluable patients was 94%, with a complete response rate of 26%. Thirty-one patients underwent local therapy following induction chemotherapy, and 25 (81%) were rendered free of disease: 14 of 15 treated with surgery and radiotherapy and 11 of 16 treated with radiotherapy alone. At a median follow-up of 11 months, 8 patients have relapsed while the remaining 17 patients continue free of disease. The dose-limiting toxicity of chemotherapy was mucositis resulting in reduction of the 5-fluorouracil dose in 28 patients. This regimen is highly effective in inducing responses in patients with locally advanced head and neck cancer; 81% of the patients who complete local therapy are rendered free of disease with this multimodal approach. Due to short follow-up, the relapse rate, overall survival, and disease-free survival cannot yet be determined.     

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.     

A phase I safety and pharmacokinetic study of OGT 719 in patients with liver cancer

OGT 719 (Oxford GlycoSciences, Abingdon, UK) is a novel nucleoside analogue with a galactose molecule attached to a fluorinated pyrimidine. OGT 719 has the capacity selectively to bind to asialoglycoprotein receptors that are found exclusively on hepatocytes and hepatocellular carcinoma (HCC) cells. The aim of this study was to establish the safety and to examine the pharmacokinetics of this novel compound in patients with liver cancer. Fourteen patients received a total of 37 cycles of OGT 719 at four dose levels ([500 mg/m² first cycle, 1 000 mg/m² subsequent cycles], 1000 mg/m², 3 300 mg/m² and 7500mg/m²). OGT 719 was administered as a 3-h intravenous infusion in a 250 ml saline solution, daily for 5 days every 4 weeks. Pharmacokinetic parameters were studied during the first cycle of dose levels 1 and 2 (500 mg/m², and 1 000 mg/m², respectively). The maximum plasma concentration was attained within 5 min of completing the infusion and almost doubled, dose dependently, with a doubling of the infused dose. The plasma level declined rapidly in a monophasic manner with an elimination half-life of 2.1 and 2.5 h for dose level 1 and 2, respectively. The mean area under the curve (AUC_o-t, area under the curve to 24 h; AUC_o-∞, area under the curve to infinity) doubled at the higher dose level. None of the patients had a significant tumor response. Elimination half-life of OGT 719 by 3-h intravenous infusion is short and monophasic. Toxicity was minimal at the highest dose level.     

Cisplatin as Second Line Chemotherapy in Advanced or Recurrent Squamous Cell Carcinoma of Head and Neck Region

Thirty-two patients with advanced or recurrent carcinoma of the head and neck were treated with cis-dichlorodiaminoplatinum II (CDDP) 75 mg/m² every third week as second line chemotherapy. The response rate was 3 per cent with one complete and no partial responders, 16 patients with no change and 10 with progressive disease. Five were not evaluated concerning response. Median time to progression was 12 weeks (confidence limits 10--17 weeks) and median survival time 21 weeks (confidence limits 10 to 33 weeks, range 4 to 109). No severe hematologic toxicity was seen. Two patients had progressive polyneuropathy, one had a severe decline in Cr-EDTA-clearance and in one decline in auditory function was suspected. It is concluded that CDDP in this schedule has no role as second line chemotherapy in advanced cancer of head and neck.