Second-line Chemotherapy In Patients Research Articles

Phase II Study of Irinotecan plus Leucovorin and Bolus 5-Fluorouracil as First- or Second-Line Chemotherapy in Patients with Advanced Gastric or Esophageal-Gastric Junction Adenocarcinoma

The aim of this study was to evaluate the activity and safety of 5-fluorouracil (5-FU) / leucovorin (LV) and irinotecan as first- or second-line treatment in patients with advanced gastric adenocarcinoma. Treatment consisted of irinotecan 80 mg/m2 intravenously (i.v.), followed by LV 200 mg/m2 (i.v.) and 5-FU 450 mg/m2 as an i.v. bolus, administered weekly for 6 weeks, followed by a 2-week rest period. Thirty-one patients (23 chemo-naïve, 8 chemo-exposed) were enrolled. The overall response rate was 22.6% and the disease control rate was 38.7%. Among the patients who received the regimen as first-line treatment, objective response rate was 30.4% and the disease control rate was 52.1%. However, progression of the disease was recorded in all the patients receiving the combination as second-line chemotherapy. The median time to disease progression (TTP) was 4 months and the median duration of survival was 7 months. The median TTP was 6 months for patients treated with first-line chemotherapy and 2.5 for those who received study treatment as second line. Furthermore, the median survival duration was 8 months and 6 months, respectively. The most frequent grade 3 toxicity was febrile neutropenia. Grade 3 non-hematological toxicities were rare. There were no treatmentrelated deaths.The combination of 5-FU/LV and irinotecan as first-line treatment was found to be well tolerated and effective in patients with advanced gastric cancer. Further investigation would be worthwhile, particularly in elderly or debilitated patients who cannot tolerate aggressive chemotherapy.

Biweekly administration of docetaxel and vinorelbine as second-line chemotherapy for patients with stage IIIB and IV non-small cell lung cancer: a phase II study of the Galician Lung Cancer Group (GGCP 013-02)

The current report aims to evaluate the efficacy and safety profile of a biweekly administration of docetaxel and vinorelbine to patients with advanced non-small cell lung cancer, who had previously been treated for this disease. In a prospective, multicenter, open-label, phase II trial, patients received 40 mg/m of docetaxel and 20 mg/m of vinorelbine on days 1 and 15, every 28 days. Treatment continued for up to a maximum of six cycles, unless disease progression or unacceptable toxicity occurred, or consent was withdrawn. Fifty patients were enrolled in the study and they received 174 cycles of chemotherapy, with a median of three cycles per patient. All patients were evaluated for efficacy and toxicity in an intention-to-treat analysis. The overall response rate was 10% [95% confidence interval (CI): 1-19], including one complete response (2%) and four partial responses (8%). Previous chemotherapy of 80% of the responders included paclitaxel. Median time to disease progression was 2.7 months (95% CI: 2.2-4.3) and median overall survival was 6.5 months (95% CI: 2.5-9.2). The survival rates at 1 and 2 years were 18% (95% CI: 7-29) and 4% (95% CI: 0-10), respectively. The most frequent severe toxicities were neutropenia (20% of patients) and leukopenia (8% of patients). Other toxicities appeared in 4% or fewer of the patients. Biweekly administration of docetaxel and vinorelbine is feasible as a second-line treatment for non-small cell lung cancer patients, but its level of activity and toxicity does not suggest any advantage compared with the results obtained with single-agent docetaxel in the same setting.

Modest efficacy of ixabepilone as second-line chemotherapy in patients with HRPC

Modest efficacy of ixabepilone as second-line chemotherapy in patients with HRPC

A phase II trial of docetaxel (Taxotere®) as second-line chemotherapy in patients with metastatic breast cancer

The efficacy and tolerability of docetaxel 100 mg/m(2) every 3 weeks as second-line chemotherapy in patients with metastatic breast cancer was investigated. In addition, the efficacy of a 3-day prophylaxis against cumulative dose-related fluid retention was examined with methylprednisolone 32 mg twice daily for 3 days starting 12 and 3 h before the docetaxel infusion together with oral cetirizine 10 mg 12 and 3 h before start of docetaxel for prevention of acute hypersensitivity reactions. According to the intent to treat-analysis 35% (95%CI: 25; 46) of the 94 patients entered responded to therapy. Their median survival was 12 months (range 0-20 months). The respective response rate for the 87 patients eligible for response evaluation was 37% (95%CI: 27; 48). Their median duration of response was 8 months (range 3-12 months), their median time to progression was 4 months (range 1-12 months). The corresponding response rate in the eligible patient cohort with anthracycline-resistant disease was 28% (95%CI: 15; 45) and increased to 44% (95%CI: 30; 59) in the cohort with non-anthracycline-resistant disease. Patients with visceral metastases responded in 36% and patients with > or = 3 organs involved in 33%. In a retrospective analysis, the 3-day premedication of corticosteroids and antihistamines proved to be as effective as the established but more toxic 5-day regimen in delaying and preventing the occurrence of docetaxel derived toxicities especially the cumulative fluid retention. In conclusion, docetaxel represents one of the most active agents for second-line treatment of metastatic breast cancer, especially for anthracycline-resistant patients. Due to comparable effectiveness of the 5-day regimen which is widely used by others and the 3-day premedication tested in this trial the latter proved to be more favourable and was therefore recommended for future therapies.

Prognostic factors for response and survival of second-line chemotherapy in patients with relapsed small cell lung cancer (SCLC)

18023 Background: Despite high response rates to initial chemotherapy, the majority of patients with SCLC experience tumor progression. Previous studies showed that both the response to initial chemotherapy and the response duration are important for predicting the efficacy of second-line chemotherapy. Therefore, relapsed SCLC is commonly classified into two groups: sensitive relapse (respond to initial chemotherapy and relapse more than 3 months after the completion of initial chemotherapy) and refractory relapse (not respond to initial chemotherapy or respond but relapse within 3 months). However, prognostic factors of the second-line chemotherapy have not been fully understood. Methods: From July 1992 to December 2003, four hundred and seventy-four patients with SCLC received chemotherapy as initial treatment, subsequently 229 patients received second-line chemotherapy (144 sensitive relapse and 85 refractory relapse) in our hospital. We analyzed the association of patients’ clinical factors with response and survival of second-line chemotherapy in sensitive relapsed patients and refractory relapsed patients, separately. For sensitive relapsed patients, analyzed clinical factors were as follows: age (<70/=70), gender (M/F), response to initial chemotherapy (CR/PR), PS at relapse (<2/=2) and the extent of disease at relapse (LD/ED). For refractory relapsed patients, analyzed clinical factors were as follows: age (<70/=70), gender (M/F), response to initial chemotherapy (responder/non-responder), PS at relapse (<2/=2) and the extent of disease at relapse (LD/ED). Results: Response to second-line chemotherapy was significantly correlated with PS in sensitive relapsed patients, however, no significant factor was detected in refractory relapsed patients. For survival, PS was the only significant prognostic factor in both sensitive and refractory relapsed patients. The median survival time was 328 days (PS<2) and 128 days (PS=2) in sensitive relapsed patients (p<0.0001), while 195 days (PS<2) and 113 days (PS=2) in refractory relapsed patients (p=0.0001), respectively. Conclusions: PS was the only significant prognostic factor for survival both in sensitive and refractory relapsed SCLC. No significant financial relationships to disclose.

Multi-center, phase II study for combination therapy with paclitaxel/doxifluridine to treat advanced/recurrent gastric cancer showing resistance to S-1: Final results (OGSG 0302)

15025 Background: We report here results of phase II study for a combination therapy with paclitaxel/doxifluridine to treat advanced/recurrent gastric cancer showing resistance to S-1. S-1 is an oral fluoropyrimidine drug that combines tegafur, CDHP, and oxonic acid (Oxo), which has been most frequently used in Japan. Methods: Subject registration was started to employ 35 patients with advanced/recurrent gastric cancer, who were selected among those with measurable lesions fitting to RECIST, and with resistant to S-1 treatment (PS, 0–2; and patient’s ages ranged from over 20 to under 75 years). We employed dosages that Hyodo et. al. used in phase I study and recommended as a standard regimen including paclitaxel, 80 mg/m2, i.v. on days 1 and 8; and doxifluridine, 600 mg/m2, p.o. on days 1–14.. These were repeated every 3 weeks. Primary endpoint of present phase II study was: RR; and secondary endpoints were OS, PFS, and onset rate of adverse events. Results: From September, 2003 to March, 2005, 35 patients were registered: including 28 men; 7 women; median age of 66 years (range, 49–75 years); and PS levels were, zero with 21 and one with 14 patients. In 33 eligible patients, except 2, clinical usefulness was evaluated resulting in response rate of 18.2% (PR, 6; SD, 15; PD, 10; and NE, 2 patients). OS was 321 days, and PFS was 119 days. Severe adverse events were found in 3 patients to discontinue the present treatment though; other adverse events were relatively mild without no death due to the present therapy. Conclusions: Patients in the present study with advanced/recurrent gastric cancer were those resistant to S-1 treatment. Response rate was 18.2% increasing to 63.6% when SD was added. OS resulted in relatively long period of 321 days, while OS from initial time starting S-1 treatment was 619 days. This suggests that the present treatment is useful as the sequential therapy. Adverse events were controllable suggesting a high reliability of the present therapy. In conclusion, the present therapy with paclitaxel/doxifluridine could be a treatment of choice as an useful second line chemotherapy for patients undergone S-1 treatment. No significant financial relationships to disclose.

Phase II study of irinotecan plus leucovorin and bolus 5 fluorouracil as first or second line chemotherapy in patients with advanced gastric or esophageal-gastric junction adenocarcinoma

15128 Background: The aim of this study was to evaluate the activity and safety of 5-fluorouracil (5-FU) / leucovorin (LV) and irinotecan as first- or second-line treatment in patients with advanced gastric adenocarcinoma. Methods: Treatment consisted of irinotecan 80 mg/m2 intravenously (i.v.), followed by LV 200 mg/m2 (i.v.) and 5- FU 450 mg/m2 as an i.v. bolus. Treatment was administered weekly for 6 weeks, followed by a 2-week rest period. Results: Thirty-one patients (23 chemo-naïve, 8 chemo-exposed) were enrolled. The overall response rate was 22.6% and the disease control rate was 38.7%. Among the patients who received the regimen as first-line treatment, objective response rate was 30.4% and the disease control rate was 52.1%. However, progression of the disease was recorded in all the patients receiving the combination as second-line chemotherapy. The median time to disease progression (TTP) was 4 months and the median duration of survival was 7 months. The median TTP was 6 months for patients treated with first-line chemotherapy and 2.5 for those who received study treatment as second line. Furthermore, the median survival duration was 8 months and 6 months, respectively. The most frequent grade 4 toxicity was febrile neutropenia. Grade 3 or 4 non-hematological toxicities were rare. There were no treatment-related deaths. Conclusions: The combination of 5-FU/LV and irinotecan as first-line treatment was found to be well tolerated, with efficacy comparable to that of other regimens in advanced gastric cancer. Accordingly, this regimen can be regarded as one of first-line options, particularly in patients who can not tolerate aggressive chemotherapy. No significant financial relationships to disclose.

The symptomatic benefit (the clinical benefit response) from the second-line chemotherapy in patients with advanced gastric adenocarcinoma

There are few reports on use of symptomatic benefits as an alternative or adjunctive for the assessment of objective response in chemotherapy of the advanced cancer. This study is performed to assess the symptomatic benefits (the clinical benefit response), in addition to the efficacy and toxicity of cisplatin plus infusional 5-fluorouracil (5-FU) combination as second-line therapy in patients with advanced gastric cancer. Fifty-eight advanced gastric cancer patients with previous chemotherapy were enrolled into the study. Cisplatin 20 mg/m(2) was given for 5 days, and 5-FU was given 1000 mg/m(2) as 20 h continuous infusion for 5 days, repeated every 28 days. The overall objective response rate was 11.3%, and overall tumour control rate was 33.9%. The clinical benefit response, in terms of weight gain, reduction in analgesic consumption and the improvement in performance status observed in 12 patients [six patients with partial response (PR) and six patients with stable disease (SD)] (22.6%), while the rates of the clinical benefit response in patients with PR and with SD were 100% and 50% respectively. Cisplatin plus infusional 5-FU combination seems to improve disease-related symptoms (clinical benefit response) of patients with advanced gastric cancer, even in patients without objective response.

Phase II study of CT-2103 as first- or second-line chemotherapy in patients with metastatic breast cancer: unexpected incidence of hypersensitivity reactions

This study evaluated the safety and efficacy of CT-2103, a novel conjugate of paclitaxel and poly-L-glutamate, in patients with HER2-negative, metastatic breast cancer who had received 0 or 1 prior lines of chemotherapy. Although CT-2103 had activity in this small study, neurotoxicity and hypersensitivity reactions were more frequent in this patient population than expected, and led to early termination of the trial. To evaluate the safety and efficacy of CT-2103, a novel conjugate of paclitaxel and poly-L-glutamate, in patients with metastatic breast cancer who had received 0 or 1 prior lines of chemotherapy. Eighteen women with HER2-negative breast cancer were enrolled. Patients received intravenous CT-2103 at a dose of 175 mg/m2 of conjugated paclitaxel over 10 min every 3 weeks, without routine premedication. Eighty-three percent of women had received prior chemotherapy as part of adjuvant (39%), metastatic (17%), or both adjuvant and metastatic (28%) treatment. Three patients (17%) had previously received a taxane in the adjuvant setting. Objective responses were observed in 4 of 18 patients (overall response rate, 22%, 95% confidence interval, 6 to 48%). Grade 3 or 4 neuropathy was observed in four patients. Grade 3 or 4 hypersensitivity reactions (HSR) were observed in four patients; none occurred prior to cycle 4 of therapy. Because of the higher-than-expected rate of HSR, the study was terminated early. Although CT-2103 had activity in this small study of women with HER2-negative metastatic breast cancer, neurotoxicity and hypersensitivity reactions were more frequent in this patient population than expected. Hypersensitivity reactions were most likely to occur in later cycles of treatment, suggesting a true drug allergy, distinct from the HSR typically seen with standard paclitaxel.

Response to Vinorelbine With or Without Estramustine as Second-Line Chemotherapy in Patients with Hormone-Refractory Prostate Cancer

Vinorelbine (VRL) in combination with estramustine has known efficacy in the initial chemotherapeutic management of hormone-refractory prostate cancer (HRPC). However, little is known about the efficacy of VRL as second-line chemotherapy in HRPC. We retrospectively identified patients with HRPC treated in a single institution with VRL as second-line chemotherapy with or without estramustine. Patient baseline characteristics, declines in prostate-specific antigen, performance status, toxicities, and survival were assessed. Thirty-nine patients were treated with VRL between 1999 and 2005. Twenty-one patients (54%) received single-agent VRL and 18 patients (46%) had concomitant estramustine. Seven patients (17.9%, 95% confidence interval 7.5%-33.6%) treated with VRL experienced prostate-specific antigen declines >or=50%. Median duration of therapy was 1.4 months (range 0.2-14.0 months). Median overall survival was 6.9 months (range 1.4-29.9 months); it was 16.1 month in responders and 5.5 months in nonresponders. Median survival was significantly longer in patients with VRL and estramustine than in patients who received VRL alone (8.5 months versus 4.1 months, P=0.05). The most common reversible adverse effect of VRL was grade 1 or 2 fatigue observed in 36% of patients. As a second-line chemotherapy, VRL demonstrated moderate activity and was well tolerated in patients with HRPC. Patients treated with the combination of VRL and estramustine experienced a longer survival than those receiving VRL alone.

Vinflunine: a new active drug for second-line treatment of advanced breast cancer. Results of a phase II and pharmacokinetic study in patients progressing after first-line anthracycline/taxane-based chemotherapy

To evaluate the single agent activity, pharmacokinetics and tolerability of the novel tubulin targeted agent vinflunine (VFL) (320 mg m−2 q 21 days) as second-line chemotherapy in patients with metastatic breast carcinoma (MBC). All patients had disease progression after anthracycline/taxane (A/T) therapy. They could have received a nonanthracycline adjuvant treatment and subsequently received a first-line A/T combination for advanced/metastatic disease; or relapsed >6 months after completion of adjuvant A/T therapy and were subsequently treated with the alternative agent; or relapsed within 6 months from an adjuvant A/T combination. Objective response was documented in 18 of 60 patients enrolled (RR: 30% (95% confidence interval (CI): 18.9–43.2%)). Among the responders, seven patients had relapsed during a period of <3 months from taxane-based regimen yielding a RR of 33.3%. The median duration of response was 4.8 months (95% CI: 4.2–7.2), median progression-free survival was 3.7 months (95% CI: 2.8–4.2) and median overall survival was 14.3 months (95% CI: 9.2–19.6). The most frequent adverse event was neutropenia (grade 3 in 28.3% and grade 4 in 36.7% of patients). No febrile neutropenia was observed. Fatigue (grade 3 in 16.7% of patients) and constipation (grade 3 in 11.7% of patients) were also common; these were non-cumulative and manageable permitting achievement of a good relative dose intensity of 93.5%. Vinflunine is an active agent with acceptable tolerance in the management of MBC patients previously treated with (A/T)-based regimens. These encouraging phase II results warrant further investigation of this novel agent in combination with other active agents in this setting or in earlier stages of disease.

Phase II Study of Pemetrexed for Second-Line Treatment of Transitional Cell Cancer of the Urothelium

To assess the antitumor activity and toxicity of pemetrexed as second-line chemotherapy in patients with locally advanced or metastatic transitional cell carcinoma (TCC) of the urothelium. Eligible patients had a performance status of 0 or 1, adequate organ function, previous treatment with one prior chemotherapy regimen for locally advanced or metastatic TCC of the urothelium or relapsed within 1 year of adjuvant or neoadjuvant treatment. Patients received pemetrexed 500 mg/m2 intravenously on day 1 every 21 days, with vitamin B12, folic acid, and dexamethasone prophylaxis. Forty-seven patients were enrolled and included in the intent-to-treat efficacy analysis. Responses: 3 (6.4%) complete responses and 10 (21.3%) partial responses produced an overall response rate of 27.7%. Ten patients (21.3%) had stable disease and 22 patients (46.8%) progressed. The median time to progressive disease was 2.9 months (95% CI, 1.7 months to 4.6 months) and median overall survival was 9.6 months (95% CI, 5.1 months to 14.6 months). Median duration of response was 5.0 months (95% CI, 3.9 months to 13.8 months). Of the 47 patients assessable for safety, grade 3 or 4 hematologic events were thrombocytopenia (8.5%; 0.0%), neutropenia (4.3%; 4.3%) and anemia (2.1%; 2.1%), respectively. Nonlaboratory toxicities included grade 4 stomatitis/pharyngitis, sepsis syndrome (one patient each), and grade 3 fatigue (three patients) and diarrhea (two patients). Single-agent pemetrexed is safe and active as second-line treatment of patients with advanced TCC of the urothelium. Additional evaluation in the first- or second-line setting in TCC of the urothelium is warranted.

Docetaxel, 5-fluorouracil and nedaplatin as second-line chemotherapy for patients with esophageal cancer after esophagectomy: A pilot study

14140 Background: We investigated the combination of docetaxel, 5-fluorouracil (5FU) and cisplatin analog, nedaplatin (CDGP) as second-line chemotherapy after esophagectomy. Methods: Eight patients with recurrent esophageal cancer who had undergone adjuvant 5FU/cisplatin after esophagectomy were included this study (7 male, 1 female; median ECOG performance status: 1). Histologic type of all esophageal cancer was squamous cell carcinoma. Patients received docetaxel 60 mg/m2 on day 1, 5FU 600 mg/m2 on days 1–5, and CDGP60 mg/m2 on day 4 every 3 weeks. A total of 17 chemotherapy cycles was administered. The median number of cycles was 2 (range 1–5). Results: The overall response rate was 62.5%. The median overall survival was 42 weeks, and the median progression-free survival was 26 weeks. Hematological and non-hematological toxicities were moderate (neutropenia WHO grade III/IV: 62.5%, alopecia grade II/III: 75%, nausea/vomiting grade II/III: 50%, neurotoxicity grade II: 12.5%). Conclusions: The combination of docetaxel, 5FU and CDGP is an active regimen with moderate toxicity in the treatment of patients with recurrent esophageal cancer. This pilot study suggests the feasibility of a combination treatment containing a taxan, 5FU and cisplatin or its analog in esophageal squmaous cell carcinoma. No significant financial relationships to disclose.

Response to second-line chemotherapy in patients with hormone refractory prostate cancer receiving two sequences of mitoxantrone and taxanes

Objectives Clinical trials have demonstrated a survival benefit with docetaxel chemotherapy, but limited data exist regarding the activity of second-line chemotherapy. Methods We retrospectively identified all patients at one institution who received at least two chemotherapy regimens for hormone-refractory prostate cancer, one mitoxantrone-based and the other taxane-based, either including docetaxel or paclitaxel. Patients were evaluated using criteria modified from the Prostate-Specific Antigen Working Group. Results A total of 68 patients were analyzed; 33 patients received mitoxantrone followed by taxane-based treatment, and 35 received taxane-based chemotherapy followed by mitoxantrone. The median patient age was 66 and 58 years and the median prostate-specific antigen at the start of treatment was 23 and 24 ng/mL in the mitoxantrone-first and taxane-first group, respectively. The response rates to taxane-based chemotherapy were greater whether it was used first or second ( P <0.0001). Progression-free survival (PFS) was longer with taxanes than with mitoxantrone, whether used first or second ( P <0.05). However, the corresponding total PFS from start of the first regimen to progression during the second regimen was similar at 39.9 and 38.7 weeks ( P = 0.67). Overall survival was also not significantly different (15.2 and 17.1 months, P = 0.97). Neither age nor the interval from diagnosis to chemotherapy influenced the differences in PFS. Conclusions Taxane-based chemotherapy is active before or after mitoxantrone. Although PFS was longer with taxane-based chemotherapy, the total PFS and overall survival were equivalent for both sequences in this retrospective analysis, suggesting that taxane-based chemotherapy retains activity, even if delayed. Although responses were seen with mitoxantrone after taxanes, the median PFS was short, and new agents are needed after taxane-based chemotherapy.

Multicenter Phase II Study of Gemcitabine and Oxaliplatin (GEMOX) as Second-Line Chemotherapy in Colorectal Cancer Patients Pretreated with 5-Fluorouracil plus Irinotecan

Purpose: To evaluate the efficacy and tolerance of the gemcitabine/oxaliplatin (GEMOX) combination as second-line chemotherapy for patients with advanced colorectal cancer (CRC) pretreated with an irinotecan (CPT-11)/5-fluorouracil (5-FU)/leucovorin (LV) regimen. Patients and Methods: Patients with documented disease progression during or after first-line treatment with CPT-11 and 5-FU/LV were enrolled. Gemcitabine (1,000 mg/m² days 1 and 8) and oxaliplatin (100 mg/m² day 1) were administered every 3 weeks. Results: Partialresponses were observed in 6 of the 34 (17.7%) patients enrolled (intention-to-treat analysis; overall response rate: 17.7%; 95% confidence interval 4.8–30.5%). Eight (23.5%) patients experienced disease stabilization and 20 (59%) disease progression (tumor growth control rate = 41.2%). The median duration of response was 5.5 months, and the median time to tumor progression 2.7 months. The median overall survival was 9.1 months (1-year survival rate: 44.0%). Grade 3 neutropenia and thrombocytopenia occurred in 18 and 15% of the patients, respectively. Other severe non-hematologic toxicities were rare. Conclusion: The interesting tumor growth control rate and the favorable toxicity profile of the GEMOX regimen in pretreated patients with advanced CRC strongly suggest that this regimen may provide an alternative therapeutic option for this group of patients.

Phase II study: combination of carboplatin and paclitaxel as second-line treatment in metastatic non-small-cell lung cancer

This study was designed to determine the efficacy and safety of the paclitaxel and carboplatin combination in second-line chemotherapy treatment of patients with non-small-cell lung cancer. Treatment consisted of 175 mg/m 2 paclitaxel infused in 1 hour and carboplatin AUC 5 infused in 30 minutes, administered each 3 weeks for a maximum of 6 cycles. The following patient groups were included in the study: those who were stage IV at diagnosis; with progression during or after the administration of previous first-line chemotherapy; PS ≤ 2 and with normal hepatic, renal and bone marrow function. Twenty-two patients were included between January 2000 and December 2002. Their clinical characteristics were: male 81% / female 19%; adenocarcinoma histology in 12 patients (55%) / squamous carcinoma in 6 patients (27%) / large cell carcinoma in 2 patients (9%), and other-types in 2 patients (9%). The Performance Status (ECOG Scale) was 0 in 5 patients (22%), 1 in 5 patients (22%) and 2 in 12 patients (55%). Previously administered treatments were: combinations with cisplatin in 11 patients (50%) and combinations without cisplatin (ifosfamide, gemcitabine, vinorelbine) in 11 patients (50%). The mean number of first-line chemotherapies received was 1 to 4 cycles in 50% patients. The mean number of second-line treatments was 1 to 3 cycles in 50% and 3 to 6 cycles in the others. The doses administered were 100% of that planned in 20 patients, with 2 patients requiring dose reductions due to neutropenia and grade 3 neurotoxicity. The treatment was well tolerated with presentation of the following grade 3-4 toxicities: neutropenia in 2 patients (9%), peripheral neuropathy in 2 patients (9%). The overall response rate was 23% (CI 95%, 8-45): 5 patients (23%) with partial response, 9 (36%) with stable disease and 8 (31%) with progression. The median time to progression with second-line treatment was 16 weeks, reaching a median overall survival of 79 weeks. From the initiation of second-line treatment median survival was 24.1 weeks (CI 95%, 13.7-34.5). In this study it was observed that the combination of paclitaxel with carboplatin as second-line chemotherapy in patients with non-small-cell lung cancer presented moderate/restrained activity without severe toxicity.

Docetaxel and mitomycin as second-line treatment in advanced non-small cell lung cancer

To evaluate the feasibility, toxicity and efficacy of the combination of docetaxel and mitomycin C as second-line chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). Thirty-eight patients with histologically confirmed, locally advanced or metastatic NSCLC were included in this phase II trial. All patients had been previously treated with a platinum-based regimen. Treatment consisted of docetaxel (75 mg/m2) followed by mitomycin C (8 mg/m2) on day 1, every 21 days. Patients received a minimum of three courses unless progressive disease was detected. A total of 190 courses of docetaxel-mitomycin C were administered (median five courses per patient). This combination was well tolerated with grade 3-4 toxicity experienced with the following frequency: neutropenia in five patients (13%), fatigue in four (11%), anaemia, thrombocytopenia, nausea/vomiting and peripheral neuropathy in one each (3%). Three of 38 patients had a partial response (8%, 95% confidence interval 2.6-21.6%), 14 patients (37%) experienced stabilization of disease and 21 (55%) had disease progression. Median time to progression was 3.6 months. Overall median survival was 10.4 months, with the 1-year actuarial survival rate being 35%. The addition of mitomycin C to docetaxel as second-line therapy in NSCLC is well tolerated but does not seem to improve the response rate.

Randomised phase II trial of gemcitabine and paclitaxel second-line chemotherapy in patients with transitional cell carcinoma (AUO Trial AB 20/99)

The objectives are to evaluate and compare the response and toxicity of a 3-weekly and a 2-weekly regimen of gemcitabine (Gem) and paclitaxel (Pac) second-line treatment in patients with transitional cell carcinoma (TCC). Between June 2000 and July 2001, 30 patients with progressive disease (PD) during first-line chemotherapy (n = 11) or relapse after adjuvant cisplatin-based chemotherapy of a metastatic or locally advanced TCC (n = 18) have been randomised to receive either six cycles (schedule A) of 3-weekly Gem (1000 mg/qm, days 1 and 8) and Pac (175 mg/qm, day 1) or 2-weekly treatment until disease progression (schedule B) with Gem (1250 mg/qm, day 1) and Pac (120 mg/qm, day 2). Restaging was performed after every 6 weeks by clinical imaging. Of 30 patients, one patient in schedule A and two patients in schedule B were not evaluable for response due to serious adverse events (SAEs) during the first cycle. The overall objective response (OR) was 44% (12 of 27) with eight complete remissions (CRs) and four partial remissions. Median time to progression (TTP) was 11 (3-41) months in schedule A and 6 (1-15+) months in schedule B. Median survival was 13 (5-46) months in schedule A and 9 (0-16) months in schedule B. Schedule A showed a significantly higher rate of CRs (7 vs. 1, p < 0.05). With a median number of six (1-6) cycles (A) and nine (1-23) cycles (B), TTP and survival were not significantly different. In schedule B, one patient had WHO grade IV anaemia and leucopenia. WHO grade III toxicities were seen in schedule A/B as follows: anaemia 3 (23%)/2 (16%) patients, leucopenia 5 (38%)/2 (16%), thrombocytopenia 0/2 (16%) and alopecia 10 (76%)/4 (32%). The combination of Gem and Pac is an effective second-line regimen in patients with mainly poor prognosis due to PD after cisplatin-based chemotherapy. Except for three SAEs (uncertainly therapy related), both regimens were tolerated well. The 3-weekly schedule with a nonsplit Pac dose showed a significantly higher complete response rate in our small study population and, thus, might be superior to the 2-weekly schedule.

Phase II Randomized Trial of Tri-weekly Versus Days 1 and 8 Weekly Docetaxel as a Second-line Treatment of Advanced Non-small Cell Lung Cancer

For orientals, titrating doses of docetaxel (60-66 mg/m(2)) have shown equal effectiveness and fewer side effects as a second-line chemotherapy for patients with advanced non-small cell lung cancer (NSCLC). Under such doses, there were no comparative data between classic tri-weekly and Days 1 and 8 weekly schedules. This Phase II randomized prospective study was designed to compare the toxicity profile, efficacy and quality-of-life (QOL) between these two schedules of docetaxel in the treatment of previously treated patients with advanced NSCLC. Fifty patients were randomized to docetaxel arm A (66 mg/m(2) Day 1) and B (33 mg/m(2) Days 1 and 8) given every 3 weeks. The overall response rates (ORRs) were 12 and 24% in arm A and B, respectively (P = 0.46), and disease control rates were 52 and 48%. The median time-to-progression (TTP) was 11.3 and 12.7 weeks and median survivals were 33.4 and 27.6 weeks, respectively. Both arms have same 1 year (36%) and 2 year survivals (12%). Arm A had significantly higher neutropenia but less compromised QOL. In this study, the response of second-line chemotherapy was significantly better in the group that was response to front-line chemotherapy (P = 0.032). While Days 1 and 8 weekly docetaxel schedules show higher ORR and less hematological toxicity, there is no advantage to tri-week schedule in terms of TTP and survival, but more compromised QOL.

Is it reasonable to consider second-line chemotherapy in patients with hormone-refractory prostate cancer?

At present, no consensus exists regarding the use of second-line chemotherapy in patients with hormone-refractory prostate cancer (HRPC). A total of 23 patients with evidence of disease progression during or after first-line chemotherapy (epirubicin, etoposide, and dexamethasone) were included in this study. Two second-line treatments were administered throughout the study period (2000-2004) with 15/23 patients receiving carboplatin AUC 3 on day 1 and vinblastine 5 mg/m2 on day 1 of a 21-day cycle and 8/23 patients treated with docetaxel 50 mg/m2 on day 1 of a 21-day cycle. The latter regimen has been used since 2003. The prostate-specific antigen (PSA) level decreased by > or =50% in 3 of 23 patients, corresponding to an overall PSA response rate of 13% (95% confidence interval, 3-34%). The median time to biochemical progression was 9, 24 and 33 weeks, respectively. The median overall survival was 39 weeks (range, 15-73 weeks) with no difference between the two chemotherapy groups (p=0.08). A significant reduction of analgesic use was observed in 2 of 10 patients (20%) who required analgesics for cancer pain upon study entry. The major toxicity was grade 3 thrombocytopenia in 2 of 23 patients (9%). Both second-line treatments, a combination of carboplatin and vinblastine and a monotherapy with docetaxel, showed modest activity at subtoxic doses in patients with HRPC.