Kansai Clinical Oncology Group Research Articles

Phase 1/2 study of concurrent chemoradiotherapy with weekly irinotecan hydrochloride for advanced/recurrence uterine cancer: A multi-institutional study of Kansai Clinical Oncology Group.

ObjectiveConcurrent chemoradiotherapy using cisplatin was thought to be standard treatment for squamous cell carcinoma of cervix, but it had not been effective for adenocarcinoma. Concurrent chemoradiotherapy using irinotecan hydrochloride (CPT-11) had been effective for colorectal cancer, thus, we chose CPT-11 as a candidate for gynecologic adenocarcinoma. To evaluate the maximum tolerated dose (MTD) of weekly CPT-11 with external pelvic radiotherapy, a phase 1/2 study was conducted according to modified Fibonacci method.MethodsEligible patients were advanced uterine cancer with measurable diseases [performance score (PS): 0−2]. Study period was from August 1st, 2002 to December 31st, 2008. The starting dose level (DL) of CPT-11 was 30 mg/m2 (DL1) given weekly for 4 weeks. Subsequently, dose escalation was scheduled in 10 mg/m2 increments to 60 mg/m2 (DL4). The fixed radiotherapy consisted of whole pelvic 1.8 Gy/d, once a day in weekday for five weeks and it amounted to 45 Gy (25 fractions) in total. ResultsSeventeen patients were enrolled. As for toxicities, one (1/17: 5.9%) grade (G) 4 neutropenia lasting 7 days had been seen in DL4. G2 diarrhea was identified in 35.3% (6/17) of the patients, and 11.8% (2/17) G3 diarrhea was observed in DL3 and DL4. Thus, the MTD of CPT-11 was defined as dose of 60 mg/m2. The recommended dose was decided as 50 mg/m2. The response rate was 88.2% [9 complete response (CR), 3 partial response (PR), 3 stable disease (SD), 2 not evaluable (NE)]. Disease control rate at 1 month after treatment completion was 100% but distant metastases were found in 24% (4/17) in longer outcome. ConclusionsMTD was 60 mg/m2 and recommended dose was set as 50 mg/m2. This concurrent chemoradiation using weekly CPT-11 was feasible at 50 mg/m2, and it might be effective even in adenocarcinoma of the uterus.

Phase II study of adjuvant chemotherapy with paclitaxel and nedaplatin for FIGO stage IB-IIA uterine cervical cancer with lymph node metastasis following radical hysterectomy: A Kansai Clinical Oncology Group study (KCOG-G1101).

e17024 Background: A multicenter phase II trial was conducted to assess the efficacy and toxicity of paclitaxel and nedaplatin as the initial postoperative adjuvant chemotherapy for high-risk uterine cervical cancer. Methods: The patients with FIGO stages IB1-IIA2 squamous cell carcinoma of the uterine cervix were enrolled. Histologic confirmation of lymph node metastasis was mandatory. Intravenous paclitaxel 175 mg/m(2) over 3hours and nedaplatin 80 mg/m(2) over 1 hour were administered on day 1 of a every 28 day cycle, of which there were 5 cycles after radical hysterectomy. Results: 62 patients were enrolled into the study protocol from November 2011 to July 2015. The median age of patients was 48.5 years (range; 28-64). Median tumor diameter was 37 mm (0-34). 10 patients (16.1%) had parametrial invasion, 44 (71.0%) had deep stromal invasion, and 53 (85.5%) had lymph-vascular invasion. 30 patients (48.4%) had one metastatic lymph node, 11 (17.7%) had two, 3 (4.8%) had three, 5 (8.1%) had four and 13 (21.0%) had five or more. With a median follow-up of 36.9 months (range: 17.2-61.5), the 2-year progression-free survival rate and pelvic disease progression-free rate were 78.9% (95% CI, 68.5% to 89.3%) and 85.0% (95% CI, 75.8% to 94.3%), respectively. The 2-year overall survival rate was 93.3% (95% CI, 86.8% to 99.8%). Adverse events were almost acceptable. Grade 3-4 adverse events (NCI-CTC ver4.0) that occurred in 5% or more patients were neutropenia (60.7%) and infection (6.6%). The proportion of patients who completed 5 cycles of treatment was 90.3%. Conclusions: Adjuvant chemotherapy with paclitaxel and nedaplatin for patients with high-risk cervical cancer after radical hysterectomy was demonstrated to be an effective and feasible treatment. Phase III trial should compare this with concurrent chemoradiotherapy. Clinical trial information: 000005605.

Phase I/II study of weekly paclitaxel and carboplatin with concurrent radiation therapy in locally advanced non-small-cell lung cancer: Kansai Clinical Oncology Group T0401

Phase I/II study of weekly paclitaxel and carboplatin with concurrent radiation therapy in locally advanced non-small-cell lung cancer: Kansai Clinical Oncology Group T0401

Validation of the distress and impact thermometer and the changes of mood during the first 6months of treatment in gynecological cancer patients: a Kansai Clinical Oncology Group (KCOG)-G1103 prospective study.

To verify distress and impact thermometer (DIT) for screening emotional distress in gynecological cancer patients by Hospital Anxiety and Depression Scale total (HADS-T) as gold standard and to assess emotional changes by DIT and HADS-T. A prospective study was conducted in newly diagnosed gynecological cancer patients during the peri-treatment period after the cancer diagnosis followed by 6-month. We defined a HADS-T score of ≥11 as being indicative of emotional distress. 117 patients were enrolled between May 1, 2011 and March 31, 2012, and 95 were eligible. The median age was 54years (range 31-77). (1) From the baseline to 3-month, distress (DIT-D) ≥4 with Impact (DIT-I) ≥2 exhibited sensitivity, specificity, positive predictive value (PPV), and negative predictive values (NPV) of 0.776 [95% confidential interval (CI) 0.688, 0.850], 0.889 (95% CI 0.824, 0.954), 0.868 (95% CI 0.792, 0.949), and 0.808 (95% CI 0.731, 0.886), respectively. (2) At 6-month, DIT-D ≥2 with DIT-I ≥1 exhibited sensitivity, specificity, PPV and NPV of 0.893 (95% CI 0.778, 1), 0.825 (95% CI 0.707, 0.942), 0.781 (95% CI 0.638, 0.928), and 0.917 (95% CI 0.826, 1). (3) At 6-month, the HADS-T, DIT-D, and DIT-I scores in individual patients were significantly reduced by a mean of 4.57 (p<0.0001), 2.34 (p<0.0001), and 1.10 (p=0.0031), respectively, compared with those scores of baseline (Student's paired t test), but still remained high. (1) On acute phase within 3-month setting, DIT; DIT-D ≥4 with DIT-I ≥2, is a reliable cut-off to screen emotional distress among gynecological cancer patients. (2) The patients' moods had improved, but not completely recovered at 6-month after the diagnosis.

Phase II study of interval debulking surgery followed by intraperitoneal chemotherapy for advanced ovarian cancer: A Kansai Clinical Oncology Group study (KCOG9812)

ObjectiveIntraperitoneal chemotherapy (IP) is known to be effective after optimal primary debulking surgery (PDS) for ovarian cancer (OC). Here, we conducted a phase II study to investigate its effectiveness after interval debulking surgery (IDS). MethodsThirty-seven patients with FIGO stage IIIB-IV and suboptimal (≥1cm diameter) residual disease after PDS were enrolled. Carboplatin (AUC 4 IV, Day 1) and cisplatin (50mg/m2 IV, Day 3) were given q21d for 3cycles. After IDS, paclitaxel (175mg/m2 IV Day 1 or 60mg/m2 IV Days 1, 8, and 15, since 2000) and cisplatin (75mg/m2 IP Day 2) were given q21d for 4cycles. The primary endpoint was progression-free survival (PFS), and secondary endpoints were overall survival (OS) and adverse events (CTCAE ver. 2.0). Clinical manifestations at first recurrence and subsequent treatment were also surveyed. ResultsOf the 37 patients, high-grade, serous adenocarcinoma was found in 33. Stages IIIB, IIIC, and IV were found in 2, 24, and 11 patients, respectively. After IDS, 23 patients had no macroscopic residual tumor. No patients had permanent enterostomy, febrile neutropenia, or platelet transfusion. The treatment protocol was completed in 22 patients, and discontinued in 5 due to IP catheter-related complications. Median PFS and OS were 22 and 57months, respectively. Among the 28 patients with recurrence, 10 had no intraperitoneal disease at first recurrence. Among the 8 patients who underwent surgical cytoreduction, 6 had no residual tumor, while 2 had a <1-cm-diameter residual tumor. ConclusionIP after IDS for patients with initially suboptimally debulked OC was effective.

Phase II trial of paclitaxel and nedaplatin in patients with advanced/recurrent uterine cervical cancer: A Kansai Clinical Oncology Group study

ObjectiveA multicenter phase II trial was conducted to evaluate the activity and toxicity of paclitaxel and nedaplatin (cis-diammineglycolatoplatonum) in patients with advanced/recurrent uterine cervical cancer. MethodsPatients were required to have measurable disease. Histologic confirmation of the primary diagnosis as uterine cervical cancer was mandatory. The treatment consisted of paclitaxel 175mg/m2 over 3hours and nedaplatin 80mg/m2 intravenously over 1hour on day 1 every 28days until progressive disease or adverse effects prohibited further therapy. ResultsFifty patients were enrolled into the study protocol from October 2007 to February 2010. 45 patients(90%) were eligible for assessment of response (RECIST version 1.0) to treatment; 31 patients (62%) received prior radiotherapy and 23 patients (46%) received prior chemotherapy. The overall response rate was 44.4% (11 complete responses and 8 partial responses) with 22.2% of patients having stable disease. Grades 3 or 4 adverse events (NCI-CTCAE ver 3) included neutropenia (n=16, 32.7%), febrile neutropenia (n=1, 2.0%), anemia (n=9, 18.4%), but there was no significant thrombocytopenia. Non-hematologic toxicity was generally not serious and without a dominant pattern. The median progression-free survival was 7.5months (95% C.I., 5.7, 9.4) and overall survival was 15.7months (95% C.I., 9.4, 21.9). ConclusionsPaclitaxel 175mg/m2 and nedaplatin 80mg/m2 intravenously on day 1 every 28days in patients with advanced/recurrence uterine cervical cancer demonstrated easy administration, favorable antitumor activity, and the toxicity profile of this regimen would be decreased compared with cisplatin-containing combinations. Evaluation of this regimen in phase III trials is warranted.

Phase II trial of paclitaxel and nedaplatin in patients with advanced/recurrent uterine cervical cancer: A Kansai Clinical Oncology Group study.

5102 Background: A multicenter phase II trial was conducted to evaluate the activity and toxicity of paclitaxel and nedaplatin (cis-diammineglycolatoplatonum) in patients with advanced/recurrent uterine cervical cancer. Methods: Patients were required to have measurable disease with adequate performance status, bone marrow, hepatic, and renal function. Histologic confirmation of the primary diagnosis as uterine cervical cancer was mandatory. The treatment consisted of paclitaxel 175mg/m2 and nedaplatin 80mg/m2 intravenously on day 1 every 28 days until progressive disease or adverse effects prohibited further therapy. Results: Fifty patients were enrolled onto the study protocol from October 2007 to February 2010. 45 patients (90%) were eligible for assessment of response (RECIST) to treatment; 31 patients (68.9%) received prior radiotherapy and 23 patients (51.1%) received prior chemotherapy. A median of four cycles were administered to each patient (range: 1-16 cycles). The overall response rate was 42.2% (11 complete responses and 8 partial responses) with 26.7% of patients having stable disease.Therapeutic benefit (CR+PR+SD) was observed in 31 (68.9%) patients. Grade 3 or 4 adverse events (NCI-CTCAE ver 3) at least possibly related to paclitaxel or nedaplatin included neutropenia (n=16, 32.7%), Febrile neutropenia (n=1, 2.0%), anemia (n=9, 18.4%), elevated serum creatinie level (n=3, 6.1%), allergy (n=1, 2.0%), anorexia (n=1, 2.0%), alopecia (n=4, 8.2%), myalgia/arthralgia (n=2,4.1%) and sensory neuropathy (n=1, 2.0%). The median progression-free survival was 4.1 months (range:1.0-33.8) and overall survival was 8.0 months (range: 1.6-33.8). Conclusions: Paclitaxel 175mg/m2 and nedaplatin 80mg/m2 intravenously on day 1 every 28 days demonstrated antitumor activity and acceptable toxicity in patients with advanced/recurrence uterine cervical cancer. Evaluation of this regimen in phase III trials is warranted.

Phase II trial of weekly irinotecan and carboplatin for relapsed ovarian cancer: A Kansai Clinical Oncology Group study.

5089 Background: Irinotecan has shown favorable activities in combination with carboplatin for patients with advanced or recurrent epithelial ovarian cancer (EOC). Thus a multicenter phase II trial was conducted to evaluate the activity and toxicity. Methods: Intravenous administrations of 60 mg/m2 of irinotecan (Days 1 and 8 ) and carboplatin at AUC of 5 mg-min/mL (Day 1), repeated every 21 days, were given to patients with either radiological or serological recurrent EOC. The primary endpoint was response rate (RR) determined by RECIST and GCIG criteria, while the secondary endpoints were adverse events (AEs; NCI-CTCAE ver 2.0) and progression-free survival (PFS). Results: From 2005 to 2009, 40 patients were enrolled in the trial. Their median age was 59 years old (range, 33-78) and histological findings were serous (68%), endometrioid (17%), and others (15%). The number of previous regimens were 1 in 45%, 2 in 30%, and 3 or 4 in 20%. 35 patients (88%) had measurable disease. Overall RR was 31% and median PFS was 5.5 months (range, 1-15) in patients with TFI <6 months, while those were 56% and 10 months (range: 3-16), respectively, in patients with TFI ≥6 months. Grade 3 or 4 toxicities encountered during the first cycle included G3/G4 neutropenia in 14/13 (68%), G3/G4 thrombocytepenia in 17/0 (43%), G3 febrile neutropenia in 2, G3 fatigue in 2, G3 nausea in 1, and G2 diarrhea in 1. Delay of the second cycle in 28 (70%), and the actual dose intensity (DI) of irinotecan and carboplatin during the first 12 weeks were 30.5 mg/m2/week (range,15-40) and 1.4 AUC of 1.4 (range 1.1-1.7), respectively. Conclusions: Our results showed that combination chemotherapy with irinotecan and carboplatin was efficacious in regard to RR and PFS. Severe hematologic toxicity was often observed, but was controllable. We concluded that the regimen was useful as second-line chemotherapy, while the recommended regimen is 60 mg/m2 of irinotecan (Days 1 and 8 ) and carboplatin at an AUC of 5 (Day 1), repeated every 28 days.

A feasibility study of carboplatin and weekly paclitaxel combination chemotherapy in endometrial cancer: A Kansai Clinical Oncology Group study (KCOG0015 trial)

A feasibility study of carboplatin and weekly paclitaxel combination chemotherapy in endometrial cancer: A Kansai Clinical Oncology Group study (KCOG0015 trial)

A feasibility study of carboplatin and weekly paclitaxel combination chemotherapy in endometrial cancer: A Kansai Clinical Oncology Group study (KCOG0015 trial)

Objectives.The optimal chemotherapy regimen for women with endometrial cancer has not been established. We assessed the feasibility, toxicity and clinical efficacy of combination triweekly carboplatin and weekly paclitaxel in women with endometrial cancer. Methods.Eligible patients had histologically confirmed primary advanced or recurrent endometrial cancer (Group A), or had localized high-risk features (Group B). All were treated with paclitaxel 80mg/m2 (days 1, 8 and 15) and carboplatin AUC 5 (day 1) each 21-day cycle. A minimum of 3 cycles was planned; if 75% or more of patients were able to receive at least 3 cycles with acceptable toxicity, the regimen was declared “feasible.” Results.Forty patients were enrolled and administered 163 cycles of therapy; 38 (95%) were chemo-naive. No patients received radiation previously. Group A (measurable disease) contained 15 patients (5 with recurrent disease, 7 receiving neo-adjuvant chemotherapy, and 3 treated adjuvantly following suboptimal cytoreduction). Group B (non-measurable disease) contained 25 patients (primary stage I:10, II:5, III:8, IV:1 and relapse 1). Hematological toxicities(G3/G4) were neutropenia (31%/33%) and thrombocytopenia (6%/0%). Reversible G3 hypersensitivity (5%) and G2 cardiotoxicity (3%) was uncommon. Thirty-one patients (78%) completed ≥3 cycles (median 4, range: 1–9). Thirteen of 15 (87%) measurable patients responded (3CR, 10PR). Eighty-seven percent of measurable patients were not progressive at 6months. In Group A, QOL scores were significantly improved after 3 cycles of chemotherapy (p=0.037), and at the completion of chemotherapy (p=0.045). QOL scores in Group B did not change during therapy. Conclusions.This combination chemotherapy is feasible and effective for endometrial cancer patients.

The current status of palliative care among Japanese gynecologists in tertiary referral hospitals: A questionnaire survey of Kansai Clinical Oncology Group (KCOG)

The current status of palliative care among Japanese gynecologists in tertiary referral hospitals: A questionnaire survey of Kansai Clinical Oncology Group (KCOG)

Phase I/II study of a docetaxel (DOC) and gemcitabine (GEM) combination for early recurrent (≤12 months)(ER) or refractory (R) epithelial ovarian cancer (EOC): Kansai Clinical Oncology Group, Japan

5046 Background:There is no standard chemotherapy regimen for EOC that does not respond to platinum-based chemotherapy (R-EOC), or responds but progresses within 12 months after completing chemotherapy (ER-EOC). Purpose: To determine the efficacy of a DOC and GEM combination for R-EOC or ER-EOC, we conducted phase 1/2 study. Methods:Between October 2000 and November 2003, R-EOC or ER-EOC patients (pts) entered this multi-institutional study. Eligible criteria: histologically verified EOC, age 16 -75 years, ECOG-PS ≤2, adequate bone marrow, hepatic, and renal function, and written informed consent. GEM was administered on days 1 and 8, and DOC on day 8. This treatment was repeated every 3 weeks. The doses were escalated as follows: dose level 1 (DL1); DOC 70 mg/m2, GEM 800 mg/m2, DL2: DOC 70 mg/m2, GEM 1000 mg/m2. Toxicities were assessed according to NCI-CTC ver2.0J and responses were assessed according to both RECIST for measurable disease and Rustin's criteria for CA125. Results:Thirty-four pts were enrolled and administered 95 cycles. The median cycle was 3 (1–7 cycles), median age was 56 years (21 to 74 years), and median interval from prior chemotherapy was 2 months (1 to 12 months). Seventeen pts received more than 3 chemotherapy regimens before the enrollment. Three pts experienced no dose-limiting toxicities (DLTs) in DL1. Two of the three pts in DL2 were experienced DLTs: febrile neutropenia grade 3 (1), and thrombocytopenia grade 4 (1). Then, 28 patients were subjected to the phase 2 study with DL1 as a recommended dose. Thirty-two patients were assessable for response. Response rate was 19.1% (6/32) with 1CR (3.1%), 5PR (16%), and 9SD(28%). One-year and 2-year survival were 51.2% and 23.4%, respectively. The median survival time was 13 months. Toxicities were mainly hematological (G3/G4): neutropenia (16%/50%), thrombocytopenia (19%/0%), anemia (13%/0%), and febrile neutropenia (3%/0%). There were no grade 3 or 4 non-hematological toxicities. Conclusions:A DOC and GEM combination for R-EOC and ER-EOC with DL1 is active and well tolerable. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eli Lilly Japan K.K.

Phase I/II study of a docetaxel (DOC) and gemcitabine (GEM) combination for early recurrent (≤12 months)(ER) or refractory (R) epithelial ovarian cancer (EOC): Kansai Clinical Oncology Group, Japan

5046 Background:There is no standard chemotherapy regimen for EOC that does not respond to platinum-based chemotherapy (R-EOC), or responds but progresses within 12 months after completing chemotherapy (ER-EOC). Purpose: To determine the efficacy of a DOC and GEM combination for R-EOC or ER-EOC, we conducted phase 1/2 study. Methods:Between October 2000 and November 2003, R-EOC or ER-EOC patients (pts) entered this multi-institutional study. Eligible criteria: histologically verified EOC, age 16 -75 years, ECOG-PS ≤2, adequate bone marrow, hepatic, and renal function, and written informed consent. GEM was administered on days 1 and 8, and DOC on day 8. This treatment was repeated every 3 weeks. The doses were escalated as follows: dose level 1 (DL1); DOC 70 mg/m2, GEM 800 mg/m2, DL2: DOC 70 mg/m2, GEM 1000 mg/m2. Toxicities were assessed according to NCI-CTC ver2.0J and responses were assessed according to both RECIST for measurable disease and Rustin's criteria for CA125. Results:Thirty-four pts were enrolled and administered 95 cycles. The median cycle was 3 (1–7 cycles), median age was 56 years (21 to 74 years), and median interval from prior chemotherapy was 2 months (1 to 12 months). Seventeen pts received more than 3 chemotherapy regimens before the enrollment. Three pts experienced no dose-limiting toxicities (DLTs) in DL1. Two of the three pts in DL2 were experienced DLTs: febrile neutropenia grade 3 (1), and thrombocytopenia grade 4 (1). Then, 28 patients were subjected to the phase 2 study with DL1 as a recommended dose. Thirty-two patients were assessable for response. Response rate was 19.1% (6/32) with 1CR (3.1%), 5PR (16%), and 9SD(28%). One-year and 2-year survival were 51.2% and 23.4%, respectively. The median survival time was 13 months. Toxicities were mainly hematological (G3/G4): neutropenia (16%/50%), thrombocytopenia (19%/0%), anemia (13%/0%), and febrile neutropenia (3%/0%). There were no grade 3 or 4 non-hematological toxicities. Conclusions:A DOC and GEM combination for R-EOC and ER-EOC with DL1 is active and well tolerable. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eli Lilly Japan K.K.

Phase II trial of weekly paclitaxel and carboplatin (wTJ) for endometrial cancer (EC): Results of a Kansai Clinical Oncology Group trial (KCOG0015) in Japan

5085 Background: The chemotherapy (CT) for recurrent or post operative high risk patients (pts) of EC has not been established. Previously, we reported the usefulness of wTJ in EC for preliminary results (Ito et al; Proc ASCO 2002). Here we report the final results. Methods: Eligibility criteria included: histologically confirmed primary advanced or recurrent EC (group A), post-operative pts having high risk factors (above FIGO stage IC, G3 histology, capillary space invasion) (group B). Each cycle considered of three-weekly drug administrations: paclitaxel 80mg/m2 on days 1, 8 and 15 and carboplatin AUC 5 on day 1 as a 1-hr infusion of each drug, and more than 3 cycles of administration were planned. Results: Between 05/2000 and 03/2002, a total of 40 pts (median age was 58, range:30 -70) were enrolled and administered 163 cycles. Thirty-six pts (93%) completed more than 3 cycles (median 4, range:1–9). ECOG performance status (PS) was 0–1 in 39 pts, PS 2 in 1 pt. Thirty-eight pts (95%) had no prior CT. Group A contained 17 pts (6 recurrent pts, 8 neo-adjuvant CT pts for bulky stage IIb –IV, and 3 pts had post operative residual tumor). Group B contained 23 pts (primary stage I:10, II:5, III:6, IV:2pts). Toxicity, response and QOL were assessed by NCI-CTC ver2.0J in all pts, RECIST in 15pts had measurable disease in group A and EORTC-QLQC30J in 19 pts obtained their approval, respectively. Hematological toxicities(G3/G4) were neutropenia (31%/33%), thrombocytopenia (6%/0%). Febrile neutropenia was not observed. Reversible G3 hypersensitivity (5%) and G2 cardiotoxicity (3%: reversible PVC) were observed. The response rate was 80% (12/15) with 3CR, 9PR and 3SD. No pts remarkably failed own QOL in this trial. Now the median follow up period of group A is 28 months (range 15–40). The median time to progression and survival are 15+ (range 5–32+) and 25+ months (range 5–40+), respectively. And the median follow up period of group B is 26 months (range 18–39). No pts relapsed and all pts are alive. Conclusions: This wTJ regimen was highly effective and feasible for EC pts. No significant financial relationships to disclose.

Phase II trial of weekly paclitaxel and carboplatin (wTJ) for endometrial cancer (EC): Results of a Kansai Clinical Oncology Group trial (KCOG0015) in Japan

5085 Background: The chemotherapy (CT) for recurrent or post operative high risk patients (pts) of EC has not been established. Previously, we reported the usefulness of wTJ in EC for preliminary results (Ito et al; Proc ASCO 2002). Here we report the final results. Methods: Eligibility criteria included: histologically confirmed primary advanced or recurrent EC (group A), post-operative pts having high risk factors (above FIGO stage IC, G3 histology, capillary space invasion) (group B). Each cycle considered of three-weekly drug administrations: paclitaxel 80mg/m2 on days 1, 8 and 15 and carboplatin AUC 5 on day 1 as a 1-hr infusion of each drug, and more than 3 cycles of administration were planned. Results: Between 05/2000 and 03/2002, a total of 40 pts (median age was 58, range:30 -70) were enrolled and administered 163 cycles. Thirty-six pts (93%) completed more than 3 cycles (median 4, range:1–9). ECOG performance status (PS) was 0–1 in 39 pts, PS 2 in 1 pt. Thirty-eight pts (95%) had no prior CT. Group A contained 17 pts (6 recurrent pts, 8 neo-adjuvant CT pts for bulky stage IIb –IV, and 3 pts had post operative residual tumor). Group B contained 23 pts (primary stage I:10, II:5, III:6, IV:2pts). Toxicity, response and QOL were assessed by NCI-CTC ver2.0J in all pts, RECIST in 15pts had measurable disease in group A and EORTC-QLQC30J in 19 pts obtained their approval, respectively. Hematological toxicities(G3/G4) were neutropenia (31%/33%), thrombocytopenia (6%/0%). Febrile neutropenia was not observed. Reversible G3 hypersensitivity (5%) and G2 cardiotoxicity (3%: reversible PVC) were observed. The response rate was 80% (12/15) with 3CR, 9PR and 3SD. No pts remarkably failed own QOL in this trial. Now the median follow up period of group A is 28 months (range 15–40). The median time to progression and survival are 15+ (range 5–32+) and 25+ months (range 5–40+), respectively. And the median follow up period of group B is 26 months (range 18–39). No pts relapsed and all pts are alive. Conclusions: This wTJ regimen was highly effective and feasible for EC pts. No significant financial relationships to disclose.

Phase II study of carboplatin and weekly paclitaxel combination chemotherapy in advanced non-small cell lung cancer: a Kansai Clinical Oncology Group study

The objective of this phase II study was to evaluate the efficacy and toxicity of carboplatin and weekly paclitaxel combination chemotherapy in previously untreated, advanced non-small cell lung cancer (NSCLC). Patients received paclitaxel at a dose of 70 mg/m 2 on days 1, 8, 15, and carboplatin with the target dose of area under the curve (AUC) of 6 on day 1 every 28 days. Forty-six patients were enrolled. A median of four cycles (range, 1–13) were administered. Complete response was observed in one patient (2.2%) and partial response in 23 patients (50%), yielding an overall intent-to-treat response rate of 52.2% (95% confidence interval, 37.8–66.6%). The median survival time was 395 days and 1-year survival rate was 51.4%. Toxicities were mild. Twelve patients (26%) had grade 3 and three patients (7%) had grade 4 neutropenia. Grade 3 thrombocytopenia was seen in four patients (8%). Massive hematoemesis due to duodenal ulcer was observed in one patient, but no other patients experienced grade 3 or more non-hematological toxicities. There was no treatment-related death. Carboplatin and weekly paclitaxel combination chemotherapy is an efficacious and feasible regimen in patients with advanced NSCLC, and this treatment will be a reasonable alternative to the conventional triweekly regimen of paclitaxel and carboplatin.

Pulmonary metastasectomy for 165 patients with colorectal carcinoma: A prognostic assessment

Objective: The purpose of this study was to analyze our entire experience with pulmonary resection for metastatic colorectal carcinoma to determine prognostic factors and critically evaluate the potential role of extended metastasectomy. Methods: We analyzed the postoperative survival of 165 patients who underwent curative pulmonary surgery at eight institutions in the Kansai region of western Japan (Kansai Clinical Oncology Group) from 1990 to 2000. Results: Overall survivals at 5 and 10 years were 39.6% and 37.2%, respectively. Cumulative survival of patients who underwent simultaneous bilateral metastasectomy was significantly lower than that of the patients who underwent unilateral metastasectomy or sequential bilateral metastasectomy (P =.048). Five-year survival was 53.6% for patients without hilar or mediastinal lymph node metastasis, versus 6.2% at 4 years for patients with metastases (P <.001). Five-year survival of patients with a prethoracotomy carcinoembryonic antigen level less than 10 ng/mL was 42.7%, versus 15.1% at 4 years for patients with a carcinoembryonic antigen level 10 ng/mL or greater (P <.0001). Twenty-one patients underwent a second or third thoracotomy for recurrent colorectal carcinoma. Overall 5-year survival from the date of the second thoracotomy was 52.1%. The 34.1% 10-year survival for the 26 patients with hepatic metastasis resected before thoracotomy did not differ significantly from that of patients without hepatic metastases (P =.38). Conclusions: The status of the hilar or mediastinal lymph nodes and prethoracotomy carcinoembryonic antigen level were significant independent prognostic factors. Patients with pulmonary metastases potentially benefit from pulmonary metastasectomy even when there is a history of solitary liver metastasis. Careful follow-up is warranted, because patients with recurrent pulmonary metastases can undergo repeat thoracotomy with acceptable long-term survival. Simultaneous bilateral metastasectomy confers no survival benefit. Prospective studies may determine the significance of this type of pulmonary metastasectomy.J Thorac Cardiovasc Surg 2002;124:1007-13