Carboplatin in Combination with Epirubicin and Cyclophosphamide in Patients with Advanced Ovarian Cancer: A phase II study

Seventy-one patients with epithelial ovarian cancer stage III (n = 56) or IV (n = 15) were treated with carboplatin 300 mg/m², epirubicin 50 mg/m² and cyclophosphamide 400 mg/m² every fourth week. Patients clinically free of tumour after six courses (n = 58) underwent a second-look laparotomy. Seventeen patients were microscopically tumour-free (24% of all) and an additional 10 (14%) had only microscopic cancer. Median time to progression was 19 months. The median survival was 33 months and the estimated 5-year survival 27%. The toxicity was mainly haematological, with leukopenia WHO grade 3-4 seen in 88% and thrombocytopenia grade 3-4 in 42% of the patients. The gastointestinal toxicity was mild and no renal toxicity was seen. This chemotherapy regimen was effective with acceptable toxicity and could be given on an out-patient basis. The possibility of increasing the efficacy and decreasing the toxicity was discussed.     

Carboplatin and vinorelbine in untreated locally advanced and metastatic non-small cell lung cancer

The aim of this study was to assess the activity and toxicity of carboplatin/vinorelbine combination chemotherapy in unresectable locally advanced and metastatic non-small cell lung cancer. Between April 1997 and June 1999 30 patients (22 M, eight F, median age 62) received treatment with carboplatin AUC 6 on day 1, and vinorelbine 25mg/m(2) on days 1, 8 and 15. Treatment was given every 28 days for six cycles unless progressive disease occurred. Twenty-three patients (77%) had stage IV disease, and seven (23%) stage IIIB. Ninety-three percent were WHO performance status 0-1. Twenty-three patients were fully assessable. Nine patients achieved partial responses (9/23, 39%) for an overall objective response rate of 9/30 (30%; 95% CI 15-49%). The median duration of response was 2.75 months (range 1-13 months). The median progression-free survival was 2 months and the median survival 5.25 months. The actuarial 1-year survival was 20%. The median number of cycles completed was two (range 1-6). Day 15 vinorelbine was administered in only 18% of cycles. The main toxicity was myelosuppression. WHO grade III/IV neutropenia was experienced in 50% of patients, however, there were only three episodes of febrile neutropenia. Eight patients required blood transfusion and one developed grade III thrombocytopenia. Treatment was ceased in one patient because of grade IV autonomic neuropathy. No patient had significant nausea and vomiting. There were no treatment-related deaths. These results indicate that carboplatin/vinorelbine is well tolerated and has similar activity to cisplatin/vinorelbine in patients with unresectable non-small cell lung cancer, however, the median survival was considerably shorter.     

Cisplatin and carboplatin combination as second-line chemotherapy in dacarbazine-resistant melanoma patients

High-dose cisplatin regimens have been shown to be highly active in advanced melanoma patients but are associated with unacceptable side effects. In order to increase the platinum dose but avoid severe side effects, we treated 15 dacarbazine (DTIC)-resistant metastatic melanoma patients with a combination regimen of cisplatin (100 mg/m2) and carboplatin (200 mg/m2), two platinum analogues with a similar mode of action but a different toxicity pattern. After a mean follow-up period of 10.7 months (range 4-18 months), two patients (13.3%) achieved complete remission and two patients (13.3%) showed partial remission, giving an overall response rate of 26.4% (95% confidence interval [CI] 4.2-49%). Furthermore, three patients (20%; 95% CI 0-40.2%) experienced stable disease. The median duration of response was 7.1 months (95% CI 4.2-10.0 months), and the median overall survival was 12.5 months (95% CI 5.8-19.2 months), with eight patients still alive. The main side effects were haematological (leukopenia/thrombocytopenia World Health Organization [WHO] grade I-IV; anaemia WHO grade I-III), gastrointestinal (WHO grade I-III), neurological (WHO grade I-II) and renal (WHO grade I) toxicity. Nevertheless, except in one patient, side effects did not result in discontinuation of therapy. Despite the small number of patients treated in this preliminary study, we believe that combining cisplatin and carboplatin represents a novel, active and well-tolerated therapeutic option as second-line chemotherapy in DTIC-resistant advanced melanoma patients.     

Combination carboplatin and radiotherapy in the management of stage II testicular seminoma: comparison with radiotherapy treatment alone.

PURPOSE: To assess the results of treatment in 33 patients with stage IIA/B seminoma who were treated with carboplatin and radiotherapy (RT) between January 1989 and December 1996. PATIENTS AND METHODS: Thirty patients received single course single agent carboplatin (400 mg/m2 or area under curve (AUC 7), two patients received two courses carboplatin, and one patient received single course carboplatin and etoposide, all 4-6 weeks prior to infra-diaphragmatic RT. Results were retrospectively compared with those obtained for 80 patients treated from 1970 to 1998 with radiotherapy alone. RESULTS: There was minimal toxicity associated with the use of carboplatin prior to RT. With a median follow-up of 4 years (range 2-70 months) 2/33 patients treated with chemotherapy and RT have relapsed, 5-year relapse free survival (RFS) = 96.9% (95% confidence interval (CI) 72.9-99.4%), and one patient has died of progressive disease, 5-year overall survival (OS) = 96.7%. With a median follow-up of 11.2 years (range 6 months to 25.8 years) 15/80 patients treated with RT alone have relapsed, 5-year RFS = 80.7% (95% CI 70.1-87.9%), including 13/61 patients treated with infra-diaphragmatic RT, 5-year RFS = 77.9%, and 2/19 treated with additional supra-diaphragmatic RT, 5-year RFS = 89.5% (P = 0.277). Eleven out of 80 patients have died, 5-year OS = 94.7%. For stage IIA, 1/14 patients treated with chemotherapy and RT have relapsed, 5-year RFS = 92.3%, compared with 5/34 treated with infra-diaphragmatic RT alone 5-year, RFS = 84.9% (P = 0.527). For stage IIB, 1/19 patients relapsed (at 69 months) following chemotherapy and RT (5-year RFS = 100%), whereas 8/27 relapsed following infra-diaphragmatic RT alone, 5-year RFS = 69.4% (P = 0.0595). CONCLUSION: Infradiaphragmatic RT alone cures the majority of patients with stage II seminoma, but the relapse rate remains high particularly for patients with stage IIB disease. As compared with historical controls, carboplatin with RT appears to reduce the relapse rate in stage II seminoma with minimal additional toxicity and the results approach statistical significance for stage IIB patients. Confirmation would require a phase III randomized comparison.     

Phase II study of paclitaxel and carboplatin in patients with advanced gastric cancer

5-Fluorouracil-based combination chemotherapy is commonly used in patients with advanced gastric cancer, but results with such therapy are fairly modest. Evaluation of newer agents is therefore required in this disease. Paclitaxel has shown promising activity as a single agent in gastric cancer. In vitro, paclitaxel exhibits sequence-dependent synergy with platinum compounds against gastric cancer. This study was conducted to evaluate the efficacy and toxicity of combination carboplatin and paclitaxel in patients with advanced gastric cancer. Twenty-seven patients with measurable or evaluable advanced gastric cancer were enrolled on the study from April 1996 to July 2000. Patients were treated with paclitaxel 200 mg/m intravenously during 3 hours followed by carboplatin at projected area under the curve 5 mg x h x ml (as per the Calvert formula). Twenty-six patients were assessable for toxicity, and 25 patients were assessable for objective response. Nine of the 27 enrolled patients had a major response for an objective response rate of 33% (95% CI 0.17-0.54) by intention-to-treat analysis. The median response duration was 4.9 months (95% CI 2.8-7.3), and median survival was 7.5 months. The 1-year survival rate was 23%. One hundred seventeen courses were administered with a median of four courses per patient administered. The major toxicity was neutropenia, with grade III to IV neutropenia observed in 9 patients (33%) and neutropenic fever in only 1 patient. Grade III peripheral neuropathy developed in two patients, and grade III myalgia and grade III fatigue developed in one patient each. There were no treatment-related deaths. The combination of carboplatin and paclitaxel is a highly tolerable, regimen with activity comparable to that of other regimens in advanced gastric cancer. This regimen needs to be further evaluated in combination with other agents and as a component of multimodality therapy in gastric cancer.     

Low-dose weekly paclitaxel as second-line treatment for advanced non-small cell lung cancer: a phase II study

PURPOSE: To assess the activity and toxicity of low-dose weekly paclitaxel in patients with non-resectable or metastatic non-small cell lung cancer (NSCLC) and who had disease recurrence or failure with previous chemotherapy. PATIENTS AND METHODS: Forty patients with NSCLC previously treated with platinum-based chemotherapy received weekly paclitaxel 80 mg/m(2) as a 1 h infusion. The median age was 63 years (range 42-77 years); 25 patients had Eastern Cooperative Oncology Group performance status (PS) 1 and 15 had PS 2. Thirty-one patients had stage IV disease and nine stage III (eight stage IIIB and one stage IIIA). RESULTS: A total of 364 weeks of treatment were administered (median 8 weeks, range 2-17 weeks). There were no episodes of grade 3 or 4 haematological toxicities. Severe non-haematological toxicity was uncommon: grade 1-2 asthenia in 50%; grade 1-2 motor neuropathy in 45% and grade 3 in 10%; grade 1-2 sensory neuropathy in 62% of patients. Alopecia was mild. The overall response rate was 37.5% (95% CI, 23.9-55): 2 CR, 13 PR, 15 SD, 8 PD, 2 NE. Median overall survival was 9.7 months (95% CI, 6.5-12.8). Median time to progression was 5.4 months (95% CI, 1.8-8.9). CONCLUSION: A low-dose weekly paclitaxel regimen had good clinical efficacy with low toxicity in this group of patients with poor prognosis. This regimen increases the therapeutic options available for second-line therapy in NSCLC patients.     

Docetaxel and carboplatin as second-line chemotherapy for metastatic non-small cell lung cancer

The aim of this pilot study was to evaluate the activity and toxicity of docetaxel plus carboplatin as second-line treatment in patients with metastatic non-small cell lung cancer (NSCLC). Patients received docetaxel 75 mg/m(2) followed by carboplatin AUC 5 on day 1 every 3 weeks in an out-patient setting. Twenty-six patients were enrolled; 23 patients were diagnosed stage IV disease and three patients had a IIIB disease with malignant pleural effusion. The median interval from first to second-line treatment was 3.5 months (range 1-13). Patients received a total of 101 cycles with a median number of four cycles per patient (range 1-6). Five patients achieved a partial remission (19.23%; 95% confidence interval (CI) 6.55-39.35%), 11 had stable disease (42.31%) and ten progressed (38.46%) after initiation of second-line therapy. Median survival was 243 days (95% CI 182-336 days), the median progression-free survival was 118 days (95% CI 89-170 days), and the 1-year survival rate was 25.98% (95% CI 6.33-45.63%). Moderate haematological and mild nonhaematological toxicities were observed. No treatment-related death occurred. In conclusion, docetaxel plus carboplatin as second-line regimen has a reasonable activity with good tolerance and encouraging survival data.     

Phase II Study with Ifosfamide,Carboplatin, Etoposide (ICE Regimen) at Intermediate Dosage for Advanced Non Small Cell Lung Cancer (NSCLC)

Abstract

We have evaluated the combination of ifosfamide, carboplatin and etoposide (ICE regimen) along with mesna in 26 previously untreated patients with non small cell lung cancer (NSCLC). Thirteen stage III B and 13 stage IV patients received intermediate doses of ifosfamide (1000 mg/m2), carboplatin (120 mg/m2) and etoposide (120 mg/m2) given intravenously on day 1 to 3 every 4 weeks. Except for one patient who experienced grade 3 transient thrombocy-topenia no major events of hematological or systemic toxicity were observed. Response rate (27%, 95% C.I., 10 to 44%), median duration of response (9 months, range 6-15), and survival (9.5 months, range 2-44+) were comparable to those achieved with conventional cisplatin-containing regimens. Our ICE combination, as compared to standard or high dose schedules appears effective, safe, well tolerated, and devoid of severe hematological toxicity.     

Dose intense triplet chemotherapy with gemcitabine, carboplatin, paclitaxel with peripheral blood progenitor cell support for six cycles in advanced epithelial ovarian cancer

The interval required for haematological reconstitution following myelosuppressive chemotherapy can be reduced by the infusion of autologous peripheral blood progenitor cells (PBPCs). When carboplatin (C) and paclitaxel (P) are followed by granulocyte colony-stimulating factor (GCSF), multiple courses can be given at 10-day intervals with the autologous PBPCs from a unit of whole blood with each cycle. We extended this approach and defined the dose-limiting toxicity and maximum-tolerated dose for the addition of gemcitabine (G) to CP for patients (pts) with EOC in a phase I-II study of increasing doses of G (0, 800, 1000 and 1250 mg x m(-2)) over four cohorts with C at area under curve (AUC) 6, plus P at 175 mg x m(-2) 3 h(-1) every 10 days for six cycles. Granulocyte colony-stimulating factor 5 microg x kg(-1) day(-1) was given s.c. days 1-10 and 450 ml whole blood was venesected before each treatment, stored untreated at 4 degrees C and reinfused 24 h later. In all, 17 patients with EOC either bulky stage IV or recurrent after treatment-free interval >12 months were treated over 30 months. Of the 17 patients, 13 completed six cycles (one patient stopped early with PD, three with toxicity), interdose interval 9-28 (median 10) days. Delays occurred in four patients due to infection or malaise, and there were no dose reductions. Haematological toxicity was not considered to be dose limiting. Febrile neutropenia was uncommon (2 patients), but grade III/IV thrombocytopenia was seen across all cohorts. Treatment was not delayed for thrombocytopenia and no bleeding complications occurred. Grade III transaminitis was seen in all patients in cohort 4 and grade IV toxicity, considered to be dose limiting, occurred in one. Responses were observed at all dose levels with six CR, seven PR, three SD and one PD. Dose intense GCP was deliverable over six cycles with manageable haematological toxicity, but with dose-limiting hepatic toxicity in cohort 4. The MTD was gemcitabine 1000 mg x m(-2), carboplatin AUC 6, paclitaxel 175 mg x m(-2) given every 10 days for six cycles.     

Single-agent paclitaxel in patients with previously untreated stage IV epithelial ovarian cancer. London Gynaecological Oncology and North Thames Gynaecological Oncology Groups.

The aim of this study was to evaluate the efficacy of high-dose paclitaxel in patients with previously untreated stage IV epithelial ovarian cancer. Paclitaxel was administered intravenously over 3 h at a dose of 225 mg m(-2) on a 21-day cycle for six courses. Thirty-six patients were entered into this study; all 36 were assessed for toxicity and 33 patients were evaluable for response. One patient had a complete response and 12 patients had partial responses (overall response rate 39.4%, 95% CI 23-58%). The overall median duration of response was 9 months (range 3.5-23+ months). The response rate to carboplatin following failure of paclitaxel within 1 year of stopping therapy was 57% (four out of seven patients). The median survival of patients was 17.2 months. The main toxicity encountered was neutropenia which was WHO grade 3 in 11 patients (31%) and WHO grade 4 in seven patients (19%). Granulocyte colony-stimulating factor (GCSF) was not given to any patient during the study. Other toxicities were: grade 3/4 infection (11%) and nausea and vomiting (11%); grade 3 bone pain (22%), fatigue (14%), diarrhoea (3%), myalgia/arthralgia (3%) and dry eyes (3%). Transient peripheral neuropathy occurred in 16 patients (44%), and alopecia was encountered in most patients (grade 2/3, 78%). Paclitaxel given at 225 mg m(-2) to patients with stage IV epithelial ovarian cancer is active, well tolerated and does not require GCSF support.     

Twelve-year experience with two courses of adjuvant single-agent carboplatin therapy for clinical stage I seminoma.

PURPOSE: During the past 30 years, radiation therapy with 28 to 30 Gy for para-aortic and ipsilateral iliac node areas was the standard adjuvant treatment for clinical stage I seminoma after orchiectomy. However, late effects of radiotherapy prompted a search for alternative adjuvant treatment approaches, including surveillance and application of carboplatin. In this retrospective analysis, we evaluated the efficacy and toxicity of two adjuvant single-agent carboplatin courses in 107 patients who were diagnosed with clinical stage I seminoma at our study centers between 1988 and 1999. PATIENTS AND METHODS: All 107 patients (median age, 39 years; range, 24 to 63 years) received two postoperative adjuvant cycles of carboplatin (400 mg/m(2)). The pathologic tumor stage was pT1 in 84 patients, pT2 in 18 patients, and pT3 in five patients. Whole blood count and serum chemistry were evaluated weekly during treatment to assess hematologic and nonhematologic toxicity. RESULTS: Six patients died from tumor-unrelated causes. The remaining 101 patients are currently alive and free of disease after a median follow-up of 74 months (range, 5 to 145 months). A detailed analysis of hematologic toxicity showed only World Health Organization (WHO) grade 1 leukocytopenia in 10.7% of all cycles and WHO grade 2 leukocytopenia in 2.1% of all cycles. CONCLUSION: Regarding the absence of tumor recurrences in our retrospective analysis and the favorable toxicity profile with no episodes of long-term toxicity, we suggest that two adjuvant courses of single-agent carboplatin for clinical stage I seminoma patients might be equivalent to radiotherapy.     

Phase II trial of continuous infusion carboplatin, 5-fluorouracil,and radiotherapy for localized cancer of the esophagus

The aim of this study was to determine the toxicity, response rate, failure-free survival, and overall survival in a treatment program comprising continuous infusion carboplatin, short in-fusion 5-fluorouracil (5-FU) and radiotherapy for localized carcinoma of the thoracic esophagus. To be eligible, patients were required to have Karnofsky performance status greater than or equal to 60, adequate organ function, and have received no prior therapy. Planned radiation dose was 50 Gy in 25 fractions over 5 weeks. 5-FU was to be administered commencing days 1 and 29 of radiotherapy, and given at a dose of 1 g/m2/d for 4 days as a continuous infusion. Carboplatin was to commence on day 1 of radiotherapy and be given throughout the period of radiation as a continuous infusion. The starting dose of carboplatin was 28 mg/m2/d. The protocol specified a 25% dose reduction of carboplatin if more than two of the first six patients experienced dose-limiting toxicity (DLT). DLT was defined as grade IV neutropenia lasting more than 7 days, grade IV thrombocytopenia, or any grade IV nonhematologic toxicity. All 23 patients in the study received protocol radio-therapy, except one who was given an extra 10 Gy. Seven patients received carboplatin at 28 mg/m2/d and 16 received 21 mg/m2/d. Hematologic DLTs were experienced by all of the seven patients receiving the higher dose. No patients in the low-dose group experienced hematologic DLTs, and only 2 of 16 ceased chemotherapy early because of myelosuppression. Three patients in the low-dose group experienced grade IV esophagitis but were able to complete protocol radiotherapy. Apart from esophagitis, nonhematologic toxicity was generally moderate or mild. Six patients had thrombosis complicating the central venous catheters. Endoscopy was performed in 21 patients (91%), with an overall complete response rate of 65% (CI: 43-84%) for the whole group or 71% (CI: 48-89%) for the endoscopically evaluated group. Estimated median failure-free survival time was 8.9 months (CI: 7.1-12.9), and estimated median overall survival time was 21.4 months (CI: 9.6 -35.4). Carboplatin at 21 mg/m2/d as a continuous infusion may be given safely in combination with short infusional 5-FU and radiotherapy for localized carcinoma of the esophagus. This combination has resulted in response data comparable to that of larger studies of cisplatin-containing regimens and warrants further study, ideally in a phase III randomized controlled trial.     

Gemcitabine and carboplatin in patients with locally advanced or metastatic non-small cell lung cancer: a prospective phase II study

PURPOSE: The primary objective of this phase II study was to determine the tumor remission rates in previously untreated patients with advanced or metastatic non-small cell lung cancer (stage IIIB and IV), after treatment with gemcitabine plus carboplatin. Secondary objectives of this study were to determine toxicity, median survival and progression free survival in the same patient population treated with gemcitabine plus carboplatin. PATIENTS AND METHODS: Chemonaive patients with histological or cytological diagnosis of stage IIIB or IV NSCLC and Karnofsky performance status >/=60 received gemcitabine 1000 mg/m(2) over 30 min on days 1 and 8 and carboplatin AUC 5.0 over 30 min on day 1 after the gemcitabine infusion. Treatment cycles were repeated every 21 days for a maximum of six cycles, or until disease progression or unacceptable toxicity occurred. RESULTS: Of the 60 patients qualified for efficacy analysis, five achieved complete remissions, 15 partial remissions and 33 had stable disease, for an overall objective response rate (CR+PR) of 33.3% (95% CI, 21.7-46.7%). Four patients had progressive disease. The predominant toxicity was hematologic, with grade 3/4 leucopoenia being most common (35% patients). The median duration of response was 5 months, median time to progression was 6 months and median survival was 9 months with 80% of patients censored. CONCLUSION: Gemcitabine plus carboplatin is an effective and well tolerated treatment for advanced NSCLC.     

Concurrent chemoradiotherapy with carboplatin and docetaxel for stage III non-small-cell lung cancer

The efficacy and toxicity of concurrent chemoradiotherapy with carboplatin (AUC=5) +docetaxel (70 mg/m(2)) were analyzed retrospectively in 20 patients with stage III non-small-cell lung cancer (NSCLC). The median age of the patients was 65 years (range, 53-73 years). The performance status (ECOG), clinical stage, and tumor histology of the patients were as follows: PS: PS 0, 12 patients; PS 1, 8 patients; disease stage: stage III A, 6 patients; stage III B, 14 patients; tumor histology: adenocarcinoma, 11 patients; squamous cell carcinoma, 6 patients; large cell carcinoma, 3 patients. The median number of treatment courses administered was 4. The median survival time was 23 months, and the 2-year survival rate was 50%. The median progression free survival was 17.5 months. The response rate was 75%. Common toxicities included grade 3/4 neutropenia (95%), grade 3 esophagitis (5%), grade 3 anorexia (30%), grade 3 febrile neutropenia (35%) and grade 5 radiation pneumonitis (5%). Further studies are warranted to evaluate the efficacy and toxicity of this regimen.     

A phase I/II study of leucovorin, carboplatin and 5-fluorouracil (LCF) in patients with carcinoma of unknown primary site or advanced oesophagogastric/pancreatic adenocarcinomas.

Carcinoma of unknown primary site (CUPS) accounts for 5-10% of all malignancies. Forty patients with metastatic CUPS or advanced oesophagogastric/pancreatic adenocarcinomas were recruited. Eligibility included ECOG performance status 0-2, minimum life expectancy of 3 months and measurable disease. The regimen consisted of bolus intravenous 5 fluorouracil (5-FU) and leucovorin (20 mg m-2) days 1-5 and carboplatin (AUC5) on day 3. The leucovorin/carboplatin/5-FU (LCF) was repeated every 4 weeks. The starting dose of 5-FU was 350 mg m-2 day-1 with escalation to 370 and then 400 mg m-2 day -1 after the toxicity at the previous level had been assessed. The maximum tolerated dose (MTD) was defined as the dosage of 5-FU that achieved 60% grade 3/4 toxicity. In addition, objective and symptomatic responses, quality of life and survival were assessed. The MTD of 5-FU in the LCF regimen was 370 mg m-2. The predominant toxicity was asymptomatic marrow toxicity. The 350 mg m-2 level was then expanded. There were two toxic deaths due to neutropenic sepsis, one at 370 mg m-2 after one course and one at 350 mg m-2 after four courses. The objective response rate was 25% with one complete response (CR) and nine partial responses (PRs). The median duration of response was 3.4 months (range 1-10). The CR and eight of the nine PRs were in CUPS patients. Twelve patients developed progressive disease on LCF. Median survival for all 40 patients was 7.8 months (10 months median survival for those treated at 350 mg m-2). The majority of patients described a symptomatic improvement with LCF chemotherapy. The recommended dose of 5-FU for future studies is 350 mg m-2 combined with leucovorin 20 mg m-2 and carboplatin (AUC5).     

A phase II feasibility study of carboplatin followed by sequential weekly paclitaxel and gemcitabine as first-line treatment for ovarian cancer

A total of 53 women with chemotherapy-na?ve stage Ic-IV ovarian cancer were treated with four cycles of carboplatin area under the curve 7 every 3 weeks, followed by four cycles of paclitaxel 70 mg m(-2) (days 1, 8, and 15) and gemcitabine 1000 mg m(-2) (days 1 and 8) every 3 weeks. In all, 37 (70%) had stage III/IV disease, with 22 (42%) having tumour >2 cm; 38 patients (72%) completed all planned treatment; 27 of the 32 (84%) patients with radiologically evaluable disease had partial or complete responses; and 30 of the 39 patients (77%) with elevated cancer antigen (CA) 125 had a greater than 75% fall in this value. At a median follow-up of 28 months, 31 patients had relapsed with a median progression-free survival of 19.5 months. In total, 79% of patients were alive at 2 years. Common Toxicity Criteria grade 3/4 haematological toxicity, predominantly neutropenia, was seen in 57% of the patients. A certain degree of pulmonary toxicity was observed; eight patients had symptomatic breathlessness, +/- decreased diffusing capacity of the lung for carbon monoxide, and interstitial chest X-ray changes during the weekly phase. In all cases, this toxicity was reversible. No significant neurotoxicity was seen. This regimen is generally well tolerated with encouraging efficacy. However, the observation of pulmonary toxicity, potentially a feature of the weekly taxane-gemcitabine regimen, was of some concern. Alternative schedules, including 3-weekly taxanes, are currently being evaluated.     

Phase I and II trials of vinorelbine with carboplatin for patients 75 years of age or older with previously untreated non-small-cell lung cancer

BackgroundThe safety and efficacy of platinum-based combination chemotherapy for elderly patients with advanced non–small-cell lung cancer (NSCLC) remains unclear. We conducted phase I and phase II trials of a combination of vinorelbine and carboplatin for patients ≥75 years of age and with advanced NSCLC.Patients and MethodsPreviously untreated patients (≥75 years of age) with stage IIIB or IV NSCLC were enrolled. Based on a 4-week cycle, vinorelbine was given on days 1 and 8, and carboplatin was given on day 1. Dose-limiting toxicity was defined as grade 4 hematologic toxicity that lasted 4 days or more, febrile neutropenia; grade 3 or worse nonhematologic toxicities; or the omission of vinorelbine administration on day 8 in the first cycle.ResultsThirteen patients were enrolled in phase I. dose-limiting toxicity was grade 4 neutropenia that lasted 4 days or more, observed in 2 of 4 patients at level 4. Phase II study used the dose of level 3 (20 mg/m² vinorelbine, area under the curve of 4 mg/mL/min carboplatin). Forty-two patients were enrolled. The response rate was 14.6% of 41 assessable patients (95% CI, 3.8-25.4). The median time to progression was 98 days (95% CI, 61-135 days), and the median survival time was 366 days (95% CI, 321-411 days). All toxicities were mild and manageable.ConclusionUse of 20 mg/m² vinorelbine on days 1 and 8, followed by carboplatin area under the curve of 4 mg/mL/min on day 1 every 4 weeks warrants a phase III study for elderly patients with advanced NSCLC.     

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.     

Carboplatin in combination with etoposide in inoperable non-small-cell lung cancer (NSCLC)

Carboplatin, a second generation platinum complex, is less nephrotoxic and emetogenic than its parent compound. We have tested the objective response to and the toxicity of the combination carboplatin 330 mg m-2 on day 1 with etoposide 120 mg m-2 on days 1, 3 and 5, administered every 3 weeks in histologically proven inoperable non-small-cell lung cancer (NSCLC) patients with a good performance status. Thirty-one patients entered the study; 29 were evaluable for response, 24 after 3 courses and 5 after 2 courses of chemotherapy. An overall response rate of 21% was found including zero complete response and 6 partial responses. In addition, 3 minor responses (10%), 12 stable diseases (38%), and 9 progressive diseases (39%) were observed. The median survival was 48 weeks, including 68 weeks for non-metastatic (M0) patients and 27 weeks for metastatic (M+) patients. This regimen was well tolerated. Gastrointestinal toxicity never exceeded WHO grade II and renal function remained in the normal range for all cases. Haematological toxicity was low in the majority of the cases; nevertheless it proved to be the dose limiting toxicity as illustrated by two grade III anemia, one grade III leucopenia, one grade III and one grade IV thrombocytopenia. Carboplatin-etoposide combination is not more active, but clearly much less toxic than cisplatin-etoposide in NSCLC.