Biomedical subjects

D Skarlos

Publications and source records attributed to D Skarlos.

At least 55 records · Page 3Linked to original sources

PubMed1998

Tropisetron in the prevention of acute nausea and vomiting in patients treated with high dose epirubicin.

Tropisetron is a novel selective antagonist of the type-3 serotonin (5-HT3) receptor, with proven efficacy in the control of emesis related to cancer treatment. Epirubicin in doses of > 100 mg/m2 has a high emetogenic potential. This study was designed to determine whether a single intravenous administration of tropisetron could prevent acute nausea and vomiting in patients treated with high dose epirubicin. Forty chemotherapy naive breast cancer patients treated with epirubicin at a dose of 110 mg/m2 on an outpatient basis were enrolled in the study. Tropisetron 5 mg i.v. was used as antiemetic prophylaxis. "On demand" treatment with tropisetron 5 mg p.os was used for the rescue of patients who failed on the initial i.v. dose. Complete control of acute nausea and vomiting had 62.5% (95% C.I. 47.2-77.8), partial control 15% (95% C.I. 3.8-26.2) and 22.5% (95% C.I. 9.3-35.7) insufficient control or failure. Headache was the most common adverse event reported in 3 patients (7.5%) and constipation in 2 patients (5%). Interestingly, patients with a negative experience of nausea and vomiting during pregnancy and those treated for metastatic disease, had a better control of chemotherapy-induced nausea and vomiting. In conclusion, a single 5 mg i.v. dose of tropisetron is safe and effective in preventing acute emesis in patients treated with high dose epirubicin.

Acute Disease↗

PubMed1997

Long-term survival data and prognostic factors of a complete response to chemotherapy in patients with head and neck cancer treated with platinum-based induction chemotherapy: a Hellenic Co-operative oncology Group study.

A group of 154 patients with locally advanced head and neck cancer, treated with platinum-based induction chemotherapy, were followed up for 5 years and several pretreatment characteristics were analyzed for possible correlation to a complete response (CR) to chemotherapy, time to progression (TTP) and overall survival (OS). Clinical stage (p = 0.0024) and a history of smoking (p = 0.0125) were selected as important prognostic factors for CR by step wise logistic regression. We also identified response to chemotherapy (p = 0.0120), age (p = 0.0066), clinical stage (p = 0.0363), N stage (p = 0.0028), and tumor grade (p = 0.0101) as significant prognostic variables for TTP. Response to chemotherapy (p < 0.0001) and age (p = 0.0017) were found also significant for OS. These long-term prognostic factors which retain their prognostic significance after several years of follow-up could be helpful in the design of future trials in this patient population.

Adolescent↗

PubMed1997

Paclitaxel by 3-h infusion and carboplatin in anthracycline-resistant advanced breast cancer. A phase II study conducted by the Hellenic Cooperative Oncology Group.

37 patients with advanced breast cancer resistant to anthracyclines were treated with paclitaxel 200 mg/m2 by 3-h infusion and carboplatin at an area under the curve of 7 mg.min/ml every 4 weeks with G-CSF support. There were 5 (14%, 95% CI 3-25%) complete and 11 (30%, 95% CI 15-45%) partial responders. Median duration of response was 11.5 months (range 5.2-16.8+), median time to progression 8 months (range 0.26-16.8+) and median survival 12 months (range 0.5-19.6+). Grade 3-4 leucopenia (27%), thrombocytopenia (10%) and diarrhoea (5%) were noted. In conclusion, the combination of paclitaxel and carboplatin is active and well tolerated in patients with advanced breast cancer resistant to anthracyclines.

Adolescent↗

PubMed1997

Paclitaxel and carboplatin in inoperable non-small-cell lung cancer: a phase II study.

BACKGROUND: Based on the high activity of single-agent paclitaxel and the superior one-year survival rates of patients with non-small-cell lung cancer (NSCLC) treated with carboplatin, a phase II trial was initiated using both agents in patients with inoperable stages III and IV disease to investigate the efficacy and toxicity of the combination. PATIENTS AND METHODS: Since July 1995, 60 patients fulfilling all eligibility criteria entered this study. All patients received paclitaxel 175 mg/m2 as a three-hour infusion, and carboplatin dosed to an area under the concentration-time curve of seven, every three weeks. No granulocyte colony-stimulating factor was given. Of the 56 male and four female patients, the median age was 57 years (range 29 to 75 years) and the median Eastern Co-Operative Oncology Group performance status was one. Most of the patients had stage IV (34) adenocarcinoma (31) with low differentiation (28). The median number of chemotherapy cycles was three, with a range of one to eight. RESULTS: Of 55 evaluable patients, 15 (27.3%) achieved partial responses, 15 (27.3%) had stable disease, and 25 (45.4%) had progressive disease. The median survival was 8.95 months and 21.6% of the patients survived more than one year. Grade 2/3 nonhematologic toxicity included alopecia (59%), neurotoxicity (3%), and myalgia/arthralgia (10%). Grade 2/3 neutropenia occurred in 14% of patients, whereas grade 3/4 thrombocytopenia was seen in only 4%. One patient died of complications of a severe allergic reaction. CONCLUSION: Combination treatment using paclitaxel and carboplatin is active and well tolerated in patients with inoperable non-small-cell lung cancer. The dose-response relationship to paclitaxel and results of comparison with other platinum-based regimens remain to be determined.

Adult↗

PubMed1997

A randomized study of epirubicin monotherapy every four or every two weeks in advanced breast cancer. A Hellenic Cooperative Oncology Group study.

PURPOSE: To evaluate the impact on the response rate in patients with advanced breast cancer (ABC) of the doubling of the dose intensity (DI) of epirubicin monotherapy. PATIENTS AND METHODS: From January 1991 until April 1996, 167 patients with ABC were randomized to receive epirubicin (110 mg/m2) either every four (81 patients, group A) or every two weeks (86 patients, group B). Filgrastim (5 micrograms/kg/daily) was administered prophylactically on days 2-12 of each cycle. RESULTS: The two groups were equally balanced in terms of major patient and tumor characteristics. Even though the median cumulative dose of epirubicin was identical in the two groups (651 mg/m2), the median DI of epirubicin was doubled in group B (27.2 vs. 52.9 mg/m2/wk, respectively). The complete response (CR) rate was significantly increased in group B (5%, 95% CI: 0.16%-9.84% vs. 17%, 95% CI: 8.9%-25.08%, P = 0.011), although overall response rates were similar (49% vs. 53%, P = 0.5957). Also, there was no significant difference in the incidence of grade 3-4 toxicity between the two groups. After a median follow-up of 25 months (range, 0.43-43.3+) no significant difference was observed in the duration of response (median, 10 months vs. 8.5 months, P = 0.5130), time to progression (median, 7.2 months vs. 7.4 months, P = 0.2970) or survival (median, 14.6 months vs. 14.9 months, P = 0.4483). Logistic regression analysis showed that performance status was a significant variable for response (P = 0.0068) and multivariate analysis using the Cox proportional hazards model revealed that performance status was significant for survival (P = 0.0049), while the presence of multiple metastases (P = 0.0020) was significant for time to progression. CONCLUSION: Doubling the planned DI of epirubicin monotherapy significantly increases the CR rate but has no influence on time to progression or survival in patients with ABC.

Adult↗

PubMed1997

Paclitaxel by three-hour infusion and carboplatin in advanced carcinoma of nasopharynx and other sites of the head and neck. A phase II study conducted by the Hellenic Cooperative Oncology Group.

BACKGROUND: Paclitaxel has been demonstrated to have significant activity in recurrent or metastatic head and neck cancer (HNC). In addition, the combination of paclitaxel and cisplatin is active in untreated patients with inoperable HNC. Substitution of carboplatin for cisplatin allows the treatment to be delivered on an outpatient basis. PURPOSE OF THE STUDY: To evaluate the activity and toxicity of the combination of paclitaxel by three-hour infusion and carboplatin as first-line chemotherapy in patients with recurrent or metastatic HNC. PATIENTS AND METHODS: From March 1994 until August 1996, 49 patients with recurrent or metastatic HNC were treated with paclitaxel (200 mg/m2, by three-hour infusion) followed by carboplatin at an AUC of 7 mg.min/ml, every four weeks. G-CSF was administered prophylactically on days 2 to 12 of each cycle. There were 41 men and 8 women with a median age of 57 years (range 23-73). The majority of the patients were symptomatic and they had recurrent disease locoregionally. Fourteen patients had nasopharyngeal cancer (NPC) and 35 had squamous cell cancers of other areas of the head and neck region (non-NPC). RESULTS: At the completion of treatment, two patients with NPC demonstrated complete and six partial responses for an overall response rate of 57% (95% CI 29%-82%). Among patients with non-NPC, the response rate was 23% (95% CI 9%-37%). After a median follow up period of 15 months, the median time to progression was 4.3 months in the non-NPC group and 16.5 months in the NPC group. At the time of the analysis, median survival had not been reached in NPC while it was 7.3 months in non-NPC patients. Grade 3-4 toxicities included anemia (2%) and leukopenia, thrombocytopenia, stomatitis, nausea/vomiting and diarrhea (4% each). CONCLUSIONS: The combination of paclitaxel and carboplatin appears to be well tolerated but only moderately active in patients with advanced non-NPC of the head and neck region. However, its activity appears promising in NPC and deserves further investigation.

Adult↗

PubMed1997

5-Fluorouracil, interferon-alpha-2b and cisplatin (FAP) for advanced urothelial cancer. A phase II study. Hellenic Co-operative Oncology Group.

PURPOSE: To evaluate the efficacy and toxicity of the FAP combination chemotherapy as first-line treatment in advanced urothelial cancer. PATIENTS AND METHODS: Thirty-four patients with histologically confirmed advanced urothelial cancer, with measurable disease and without previous chemotherapy entered the study; all 34 are evaluable. The 28 males and 6 females had a median age of 65 (19-75) and a median ECOG performance status of 1 (0-2). Twenty-eight patients had bladder cancer, four had renal pelvic cancer and two ureteral cancer. Thirty patients had transitional cell carcinoma and four mixed, mostly of grade 3. Sites of disease included lymph nodes (18), bladder (9), liver (9), pelvic mass (9), lung (7), etc. The treatment plan was as follows: 5-fluorouracil 500 mg/m2 continuous infusion D1-D5 and D22-D26; interferon-alpha-2b 5 million i.u./m2 D1-D5 followed by 3x/week and then D22-D26; cisplatin 25 mg/m2 D1, D8, D15, D22. Cycles were repeated every 36 days. RESULTS: The median number of cycles administered was 3 (1-6). The relative dose intensities for 5-fluorouracil, interferon and cisplatin were 76%, 71% and 75%, respectively. Twenty-two of 34 patients (65%, 95% confidence interval [95% CI], 46% to 80%) had objective responses, including six complete clinical responses (CR) (18%, 95% CI, 7% to 35%) and 16 partial responses (PR) (47%, 95% CI, 30% to 65%). Three patients had stable disease and seven progressed. Two patients discontinued treatment after the first cycle because of toxicity. The median survival is 15.30 months (1.40-37.60), the median time to progression 11.60 months (4.13-37.60), and the median survival of complete responders 20.75+ months (8+ to 38+). The only significant hematologic toxicity was the grade 3-4 neutropenia in 44%. Non-hematologic toxic effects were unremarkable. CONCLUSION: The FAP combination as first-line chemotherapy is highly active in the treatment of advanced urothelial cancer, and has limited toxicity. Further phase III studies are in progress to compare FAP and M-VAC.

Adult↗

PubMed1997

Paclitaxel and carboplatin in recurrent or metastatic head and neck cancer: a phase II study.

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) appears to be one of the most active drugs in the treatment of advanced head and neck cancer. The maximum tolerated dose of paclitaxel in combination with carboplatin is currently being evaluated in phase I/II studies. We designed a phase II study to evaluate the activity and acute and cumulative toxicity of this combination in patients with recurrent or metastatic cancer of the head and neck. Chemotherapy consisted of paclitaxel 200 mg/m2, given as a 3-hour infusion, and carboplatin dosed to an area under the concentration-time curve of 7 mg x min/mL, administered every 28 days. Granulocyte colony-stimulating factor (5 microg/kg) also was given on days 2 to 12 of each cycle. At the time of this report, 41 patients had entered this study. Primary sites included the nasopharynx (10 patients), larynx (18), oral cavity (three), oropharynx (six), hypopharynx (three), and unknown (one). Among 25 evaluable patients with non-nasopharyngeal cancer, there were two complete responses and three partial responses, for an overall response rate of 20% (95% confidence interval, 4% to 36%). Among eight evaluable patients with nasopharyngeal cancer, four achieved a complete response and two a partial response. Grade 3 to 4 toxicities included anemia (2.5%), leukopenia (7.5%), thrombocytopenia (5%), vomiting (5%), stomatitis (2.5%), and infection (5%). These preliminary data indicate that the combination of paclitaxel and carboplatin is active against advanced head and neck cancer, particularly when used in the treatment of nasopharyngeal cancer.

Adult↗

PubMed1997

Intensified carboplatin regimen with GM-CSF support in non-small cell lung cancer (NSCLC). A Hellenic Co-operative Oncology Group Study (HeCOG).

This is a continuation of a HeCOG previous trial utilizing carboplatin and vindesine in conventional doses as a non-toxic regimen provided easily on an outpatient basis in NSCLC. In the present study we investigated whether an intensified dose-carboplatin could yield a better response. Carboplatin at a dose of 450 mg/m2 dose in combination with vindesine 3 mg/m2 every three weeks and GM-CSF support was used in a phase II study to treat 44 patients with non-small cell lung cancer (NSCLC). As compared to our previous study carboplatin dose intensity was increased from 75 mg/m2/wk to 150 mg/m2/wk. Six patients (13.6%) responded to treatment and all were partial responders. The median duration of response was 5 months (range 1.5-9 month). After a retrospective analysis a dose response effect was not evident at different carboplatin AUC doses. Twenty patients (45.45%) experienced thrombocytopenia and seventeen patients (38.6%) anemia as major toxicities. This study shows that in NSCLC a dose-response effect does not exist between carboplatin dose intensification and response rate cannot be traced.

Adult↗

PubMed1997

Paclitaxel (175 mg/m2) plus carboplatin versus paclitaxel (225 mg/m2) plus carboplatin in non-small cell lung cancer: a randomized study.

A recent phase II study by our group documented a response rate of 27% with the combination paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) 175 mg/m2 plus carboplatin dosed to a target area under the concentration-time curve of 7 in patients with advanced non-small cell lung cancer. In an effort to evaluate the dose-response relationship of paclitaxel with quality of life, we initiated a phase III prospective trial. Patients with inoperable non-small cell lung cancer were randomized into two groups. Group A received paclitaxel 175 mg/m2 plus carboplatin dosed to an area under the concentration-time curve of 6 every 3 weeks. Group B received the same regimen, with paclitaxel increased to 225 mg/m2. Since July 1996, 49 patients have entered the study, 29 in group A and 20 in group B. Patient and tumor characteristics were well distributed between both groups. In group A, 16 patients were evaluable, with one complete response, six partial responses, three stable disease, and six progressive disease. In group B, 12 patients were evaluable, with two partial responses, four stable disease, and six progressive disease. Treatment was well tolerated in both groups. More neurotoxicity and neutropenia were noticed with high-dose paclitaxel. There were no drug-related deaths. It is too early to draw definite conclusions regarding response and survival, but regarding toxicity, it seems that paclitaxel 225 mg/m2 plus carboplatin dosed to an area under the concentration-time curve of 6 is well tolerated without the use of growth factors. Although the results are premature, quality of life does not seem to be affected by the increased paclitaxel dose.

Adult↗

PubMed1997

Paclitaxel in combination with carboplatin or gemcitabine for the treatment of advanced head and neck cancer.

We performed a phase II study to evaluate the activity and toxicity of the combination of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and carboplatin as first-line treatment in patients with recurrent or metastatic head and neck cancer. From March 1994 until August 1996, 49 patients were treated with paclitaxel 200 mg/m2 by 3-hour infusion followed by carboplatin at an area under the concentration-time curve of 7 mg/mL x min; treatment was requested every 4 weeks. Granulocyte colony-stimulating factor was administered prophylactically on days 2 to 12 of each cycle. The study included 41 men and eight women, with a median age of 57 years (range, 23 to 73 years). Most of the patients were symptomatic and had locoregional disease. Primary sites included nasopharynx (14 patients), oropharynx (six), oral cavity (four), hypopharynx (three), larynx (20), paranasal sinuses (one), and unknown (one). After the completion of treatment, four patients (8%; 95% confidence interval, 0% to 16%) achieved a complete response and 12 (24%; 95% confidence interval, 12% to 37%) achieved a partial response. Grade 3/4 toxicities included anemia (2%) and leukopenia, thrombocytopenia, nausea/vomiting, diarrhea, and stomatitis (4% each). After a median follow-up of 15.3 months, median time to progression was 5.7 months (range, 0.5 to 29.8+ months) and median survival was 13.3 months (range, 0.5 to 30.2+ months). In our ongoing study in a similar patient population, gemcitabine was substituted for carboplatin.

Adult↗

PubMed1996

Prognostic variable in patients with advanced colorectal cancer treated with fluorouracil and leucovorin-based chemotherapy.

Possible prognostic variables for tumor response, time to progression (TTP), and survival in 141 patients with advanced colorectal cancer treated with fluorouracil and leucovorin-based chemotherapy were analyzed. None of the variables examined for their possible influence on tumor response attained significance in the stepwise logistic regression. In the univariate analysis, variables found to be strongly associated with TTP were performance status (PS) (P = 0.0301), liver involvement (P = 0.030), and the initial values of WBC (P = 0.0319), lactic dehydrogenase (LDH; P = 0.0053), gamma-glutamyl-transpeptidase (gamma-GT; P = 0.0013), alkaline phosphatase (ALP; P = 0.0186), albumin (P = 0.0004), and carcinoembryonic antigen (CEA; P = 0.0014). In the Cox analysis, liver involvement (P = 0.0553), albumin (P = 0.0181), PS (P = 0.484), and ALP (P = 0.0553) were retained as independently significant variables. When only patients with liver metastases were included in the analysis, then only albumin (P < 0.001) demonstrated a prognostic significance. Also, in the univariate analysis, variables predicting survival were PS (P = 0.0230), grade (P = 0.00600), liver involvement (P = 0.0002), LDH (P = 0.0001), gamma-GT (P < 0.001), ALP (P = 0.0006), albumin (P = 0.0309), and CEA (P = 0.005). With the multivariate analysis, gamma-GT (P = 0.0004), albumin (P = 0.0634), and CEA (P = 0.0804) were selected as significant. In those patients who presented with liver involvement, variables predicted survival were gamma-GT (P = 0.0041), albumin (P = 0.0442), and the percentage of involved liver parenchyma (P = 0.0690). These results could be helpful for the stratification of future trials in advanced colorectal cancer.

Adult↗

PubMed1996

A phase II study of paclitaxel in advanced breast cancer resistant to anthracyclines.

33 women with advanced breast cancer resistant to anthracyclines were treated with paclitaxel 175 mg/m2 in a 3 h infusion every 3 weeks. The median age was 53 years (range 30-72) and the median performance status was 1 (range 0-2). 24 (73%) patients had visceral metastases while 22 (67%) had > or = two involved sites. 23 (70%) patients received anthracycline or mitoxantrone in an adjuvant setting and 21 (64%) for advanced disease. There were two (6%, 95% confidence interval (CI) 1-20%) complete responses (CRs) and 12 (36%, 95% CI 20-55%) partial responses (PRs). Median dose intensity of paclitaxel delivered was 58 mg/m2/week. Median time to progression was 24 weeks (range 4-61) and median survival was 41 weeks (range 8-66). Grade 3-4 toxicities included leucopenia (9%), stomatitis (3%), alopecia (91%), neurotoxicity (9%), infection (3%) and diarrhoea (3%). In conclusion, paclitaxel at a dose of 175 mg/m2 exhibits significant activity in advanced breast cancer resistant to anthracyclines.

Adult↗

PubMed1996

A prospective randomized phase III study in non-small-cell lung cancer comparing cisplatin, ifosfamide, vinblastine (VIP) versus cisplatin, ifosfamide and etoposide (VIP-16). Hellenic Co-Operative Oncology Group.

BACKGROUND: It was recently reported that when ifosfamide was added to cisplatin and vinblastine the response rate was increased but not the survival in patients with non-small-cell lung cancer (NSCLC). The purpose of this study was to investigate the possibility of increased responses and survival with use of the combination of cisplatin, ifosfamide, etoposide (VIP-16) in comparison to the combination of cisplatin, ifosfamide, vinblastine (VIP) in non-operable NSCLC. PATIENTS AND METHODS: Two hundred twelve patients with histologically confirmed diagnoses of NSCLC were randomized into two groups: group A received cisplatin 100 mg/ m2, vinblastine 6 mg/m2 and ifosfamide 3 mg/m2 i.v. on day 1 every 3 weeks; group B received the same regimen except that etoposide 120 mg/m2 was substituted for vinblastine on days 1, 2, and 3. Patients were well balanced for age, sex, performance status (PS), stage, grade, histology and sites of disease, and the relative dose intensity was similar in both groups. RESULTS: One hundred one patients were evaluable for response in group A and 99 in group B. The overall response rates were 29% in group A (5CR) and 25% in group B (3CR). The median time to progression was 7.51 (2-35) months for group A and 7.7(1-28) months for group B (P = 0.34). The median survival was 8.49 (0.33-37.44) months for group A and 9.38 (0.43-36.59) for group B (P = 0.39). Multivariate Cox stepwise analysis showed stage to be the only significant prognostic factor for survival (P = 0.0114). Toxicity was not remarkable and not different between the two groups except for alopecia which was much more common in the patients who received etoposide. CONCLUSION: VIP and VIP-16 combination chemotherapies are equally active in NSCLC with acceptable toxicity. Stage proved to be the most significant prognostic factor for survival in this study.

Adult↗

PubMed1996

Recombinant interferon ALFA-2A in combination with carboplatin, vinblastine, and bleomycin in the treatment of advanced malignant melanoma.

Thirty-four patients with advanced malignant melanoma were treated with recombinant alpha-interferon (IFN) and chemotherapy consisting of carboplatin, vinblastine, and bleomycin (CVB). CVB was given for four cycles and IFN for 1 year or until progression. Of the 34 analyzed patients, 17 (50%) achieved an objective response, including two complete (6%) and 15 partial responses (44%). Responses were noted in cutaneous, lymph node, and pulmonary sites, with a median time to disease progression of 5 months (range, 3-20 months). The median survival from onset of therapy was 8 months (range, 1-22 months) for the 34 patients. Ninety-four percent of the patients experienced flu-like symptoms and 82% fatigue or weakness. Leukopenia grade 3-4 was observed in four patients (12%). There were two toxicity-related deaths (6%); one from bleomycin-induced pneumonitis and one from neutropenic sepsis. It is concluded that the addition of IFN to CVB regimen, in this study, showed no apparent advantage on response rates, disease-free interval, or survival. The observed treatment-related mortality was unacceptably high. IFN administered as maintenance therapy following CVB conferred no survival benefit.

Adult↗

PubMed1996

Fluorouracil and leucovorin with or without interferon alfa-2b in advanced colorectal cancer: analysis of a prospective randomized phase III trial. Hellenic Cooperative Oncology Group.

PURPOSE: To investigate if double modulation of fluorouracil (5-FU) with leucovorin (folinic acid [FA]) and interferon alfa-2b (IFN 2b) improves responses and survival in comparison to single modulation of 5-FU with FA. PATIENTS AND METHODS: One hundred six patients with histologically confirmed advanced colorectal cancer, measurable disease, and without previous chemotherapy were prospectively randomized into two groups. Patients in group A received 5-FU 450 mg/m2 as an intravenous bolus in the midinfusion of FA weekly. FA was given at a dose of 200 mg/m2 in 500 mL 0.9% normal saline solution in 2-hour infusion. Patients in group B received exactly the same regimen plus IFN 2b 5 million units subcutaneously three times weekly. RESULTS: All patients were well balanced in both groups regarding age, sex, performance status, number, and site of metastasis. One hundred two patients were assessable. All patients have died. There was no difference in response between the two groups (7.8% v 9.8%). Median survival was 10.1 months in group A, and 7.2 months in group B (P = .00189). Median time to progression was 8.4 and 5.2 months, respectively (P = .00196). Overall, better performance status and older age had a positive impact on survival. Toxicity was the most important and catastrophic aspect of this study. Patients who received IFN 2b had significantly worse anemia, neutropenia, diarrhea, anorexia, weight loss, flu-like syndrome, and psychological reactions. CONCLUSION: Based on this final analysis, the addition of IFN 2b to the combination of 5-FU and FA enhances toxicity and contributes to decreased survival.

Adult↗

PubMed1996

Cisplatin and continuous infusion of fluorouracil followed by radiation and weekly carboplatin in the treatment of locally advanced head and neck cancer: a Hellenic Cooperative Oncology Group study.

Induction chemotherapy followed by radiation has been extensively studied in an effort to improve local control and possibly overall survival of patients with locally advanced head and neck cancer. From June 1989 until May 1991, 39 patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) were treated with 3 cycles of induction chemotherapy, consisting of cisplatin (100 mg/m2 d 1) and fluorouracil (1000 mg/m2 d 2-6) followed by radiation potentiated by weekly administration of carboplatin (60 mg/m2). Surgery was performed in selected patients with residual disease after the combined modality approach. Four cycles of adjuvant chemotherapy with carboplatin (325 mg/m2) and bleomycin (15 u) were administered in those patients who demonstrated a partial response after locoregional treatment. There were 36 men and 3 women with a median age of 56 (range 39-74) years and Karnofsky performance status of 70 (range 60-100). The primary site of the tumor was nasopharynx (8), oropharynx (8), hypopharynx (3), oral cavity (4), larynx (13), paranasal sinus (2), and salivary glands (1). Thirty-two (82%) patients presented with stage IV disease. After the completion of induction chemotherapy, 14 (36%, 95% CI 21-53%) patients achieved a complete response (CR). This CR rate was increased to 56% (95% CI, 42-74%) after locoregional treatment. Main toxicities included nausea/vomiting (56%), leukopenia (40%), anemia (30%), thrombocytopenia (10%), stomatitis (28%), diarrhea (17%), and alopecia (12%). Median relapse-free survival was 18 (1-50) months, median time to progression was 13 (0.3-58.5) months, and median survival 19 (0.3-59) months. Induction chemotherapy with cisplatin and fluorouracil followed by radiation potentiated with carboplatin is feasible. However, this combined modality approach, as applied in the present study, does not appear to yield superior results than those reported with chemotherapy followed by radiation alone.

Animals↗

PubMed1996

Paclitaxel and carboplatin in nonoperable non-small cell lung cancer.

Based on the high activity of single-agent paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in non-small cell lung cancer (NSCLC) and the superior 1-year survival rates of patients with NSCLC treated with carboplatin, the Hellenic Cooperative Oncology Group initiated a phase II trial to investigate the efficacy and toxicity of the combination of both agents in patients with nonoperable stage III and IV NSCLC. Since July 1995, 31 eligible patients have entered into this study. All patients received paclitaxel 175 mg/m2 as a 3-hour infusion plus carboplatin dosed to an area under the concentration-time curve of 7, every 3 weeks. No granulocyte colony-stimulating factor was given. Among the 29 male and two female patients, the median age was 55 years (range, 29 to 73 years) and the median performance status was I (range, 0 to 2). Most of the patients had stage IV adenocarcinoma (19 patients), with poor differentiation (15 patients). The median number of prior chemotherapy cycles was two, with a range of one to six. Among 21 evaluable patients, seven achieved a partial response, 10 had stable disease, and four had progressive disease. It is too early for evaluation in nine patients. Grade 2/3 nonhematologic toxicities included alopecia (46.4%), neurotoxicity (3.3%), and myalgia/arthralgia (7.1%). Grade 2/3 neutropenia was experienced by 10.7% of patients, whereas grade 2 thrombocytopenia was seen in only 3.3%. One patient died following complications of severe allergic reaction. In conclusion, although this study is ongoing, it is clear that the combination of paclitaxel and carboplatin is effective and well tolerated in patients with nonoperable NSCLC.

Adult↗