A randomized phase II trial of adjuvant chemotherapy with docetaxel (DOC) plus cisplatin (CIS) versus paclitaxel (PAC) plus carboplatin (CAR) in patients with completely resected non-small cell lung cancer (NSCLC): Safety and feasibility data from trial TORG 0503

7561 Background: Adjuvant chemotherapy is standard of care for patients with completely resected stage IB, II and IIIA NSCLC. However, the optimum chemotherapy regimen has not been determined. TORG 0503 was conducted to evaluate platinum-based third generation regimens in this clinical setting. Methods: Patients with completely resected stage IB, IIA, IIB or stage IIIA NSCLC were stratified by stage (IB/IIA vs. IIB/IIIA) and institution and randomized to receive 3 cycles of DOC (60 mg/m2, day 1) plus CIS (80 mg/m2, day 1) or 3 cycles of PAC (200 mg/m2, day 1) plus CAR (AUC 6, day 1). Both regimens were repeated every 3 - 4 weeks. Other eligibility criteria included ECOG PS 0–1, age ≥20, and =<70 years old, adequate organ function, no prior chemotherapy or radiotherapy. Patients who underwent pneumonectomy were excluded. The primary endpoint was 2-year relapse free survival (RFS), and secondary endpoints were overall survival (OS), quality of life (QOL), feasibility and toxicity. Results: 111 patients were randomized between April 2006 and July 2008, 58 patients to DOC+CIS (DC) and 53 to PAC+CAR (PA). Patients’ demographics (DC/PA): median age 63/59 years, 60%/66% male, 17%/22% PS 1, 79%/73% adenocarcinoma, 40%/40% of patients were stage IB/IIA, 60%/60% IIB/IIIA. Feasibility: 93% (54/58) of patients allocated to DC and 92% (49/53) patients in the PA arm completed 3 planned cycles of chemotherapy. Toxicities: DC vs. PA: Grade (G) 3/4 neutropenia (86%/75%), G3/4 anemia (2%/0%). G 3 febrile neutropenia (10%/4%), G2 ALT (0%/10%), G2 creatinine (17%/0%), G2–4 allergy (0%/4%), G2 alopecia (43%/47%), G2/3 fatigue (5%/10%), G2/3 anorexia (43%/22%), G2/3 nausea (47%/22%), G2/3 vomiting (31%/12%), G2 diarrhea (12%/8%), G2 constipation (2%/4%), G2/3 sensory neuropathy (3%/33%), G2/3 arthralgia (0%/31%), G2 myalgia (2%/8%). No treatment related deaths were observed in either arm. Conclusions: Both docetaxel plus cisplatin and paclitaxel plus carboplatin are safe and feasible regimens as adjuvant chemotherapy. [Table: see text]

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Phase III randomized trial of definitive chemoradiotherapy (CRT) with FOLFOX or cisplatin and fluorouracil in esophageal cancer (EC): Final results of the PRODIGE 5/ACCORD 17 trial.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.18_suppl.lba4003 ◽

2012 ◽

Vol 30 (18_suppl) ◽

pp. LBA4003-LBA4003 ◽

Cited By ~ 11

Author(s):

Thierry Conroy ◽

Marie-Pierre Galais ◽

Jean Luc Raoul ◽

Olivier Bouche ◽

Sophie Gourgou-Bourgade ◽

...

Keyword(s):

Squamous Cell ◽

Treatment Options ◽

Complete Response ◽

Phase Iii ◽

Eligibility Criteria ◽

Randomized Phase Ii ◽

Secondary Endpoints ◽

Grade 3 ◽

Ecog Ps

LBA4003 Background: CRT is one of the best treatment options for localized EC. As new combinations are required to improve safety and survival, we launched a randomized phase II study to assess the complete response (CR) rate of CRT with FOLFOX versus 5FU/cisplatin in 97 pts with localized EC (Conroy 2010). The trial having met its objectives, it has been pursued as a phase III trial. Stratified randomization was performed centrally in a 1:1 ratio according to histological type, pretreatment weight loss in the prior 6 months (<10% vs ≥10%), ECOG PS (0 vs 1 vs 2), and center. Methods: Pts with technically unresectable cancer or those with surgical contraindications or who refused to undergo surgery were eligible. Eligibility criteria also included age >18 years (y), PS ≤ 2, previously untreated adenocarcinoma or squamous cell EC (any T, N0 or N1, M0 or M1a). The radiation dose was 50 Gy (2Gy/fr) 5 d/wk for 5 wks in both arms. In Arm A, pts received 6 bimonthly cycles (cy): oxaliplatin 85 mg/m2 d1 and leucovorin 200 mg/m2 followed by 5-FU 400 mg/m2 bolus d1 then 1,600 mg/m2 46h continuous infusion (ci) ; the first 3 cy were delivered during RT, the 3 other after. In Arm B, pts received 4 cy: cisplatin 75 mg/m2 d1 followed by 5FU 1,000 mg/m2/d ci d1-4, the first 2 cy during RT and 2 other after. The primary endpoint was PFS. Main secondary endpoints were OS, grade 3-4 toxicities, and quality of life. A total of 266 pts would provide 90% power to detect a 20% 3y-PFS difference (α=0.05). Results: 267 pts were enrolled between 10/2004 and 08/2011. Treatment cohorts were well balanced: male 81%; median age 61 y; PS 0 53%, squamous cell 85.8%, stage III 52%, IVA 6.0% and IVB 3.0%. Full treatment was delivered to 67.9% and 72.2% of pts in arms A/B, respectively. 7 toxic deaths occurred in each arm. Grade 3/4 toxicities per pt (%) in arms A/B were neutropenia 30.6/31.3, febrile neutropenia 5.3/7.0, anemia 5.4/11.0, asthenia 17.6/10.2, respectively. The median FU time was 25.3 mos. 3y-PFS was 18.2/17.4 % (HR=1.07; 95%CI =0.80-1.43) and median OS was 20.2 /17.5 m (HR=1.06; 95%CI =0.77-1.46). Conclusions: CRT with FOLFOX does not improve PFS compared to cisplatin and 5-FU and has similar toxicities.

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Phase II trial of adjuvant mFOLFOX6 after metastasectomy for pulmonary metastasis of colorectal cancer: WJOG5810G.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.4097 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 4097-4097

Author(s):

Nozomu Machida ◽

Takehiro Okumura ◽

Junji Kishimoto ◽

Narikazu Boku ◽

Tomohiro Nishina ◽

...

Keyword(s):

Colorectal Cancer ◽

Adjuvant Chemotherapy ◽

Pulmonary Metastasis ◽

Disease Free Survival ◽

Sensory Neuropathy ◽

Eligibility Criteria ◽

Phase 2 Trial ◽

Grade 3 ◽

Ecog Ps ◽

Peripheral Sensory

4097 Background: Resection of pulmonary metastasis (PM) is widely accepted to improve the prognosis in selected patients (pts) with metastatic colorectal cancer (CRC). However, the clinical implication of adjuvant chemotherapy after metastasectomy of PM is unknown. We conducted a multi-center phase 2 trial of adjuvant chemotherapy with mFOLFOX6 after metastasectomy of PM-CRC. Methods: Main eligibility criteria were first curative metastasectomy of 4 or less PMs and no prior chemotherapy except for adjuvant chemotherapy with fluoropyrimidine monotherapy after curative resection of primary or extrathoracic CRC metastasis. The study treatment was 12 courses of mFOLFOX6 (oxaliplatin 85 mg/m2, l-leucovorin 200 mg/m2, 5-fluorouracil 400 mg/m2 bolus followed by 2400 mg/m2 continuous infusion, every 2 w). The primary endpoint was overall survival (OS). The secondary endpoints included disease-free survival (DFS), adverse events (AEs), and recurrence sites. The sample size was determined to be 93 expecting 5-year OS rate of 50% with threshold 35% (90% power, alpha error 5%). Results: Fifty-two pts from 34 institutions were enrolled between July 2011 and July 2014. Patient enrollment was closed prematurely because of slow accrual. Four patients were ineligible after enrollment and the safety and efficacy cohort comprised 52 and 48 patients, respectively. Patient backgrounds were as follows: gender (male/female) 31/21, median age (range) 63 (42-75) years, ECOG PS (0/1) 48/4, primary site (colon/rectum) 18/34, number of PM (1/2/3/4) 36/9/5/2, synchronous/metachronous PM 11/41, and unilateral/bilateral PM 40/12. With the median follow-up time of 6.0 (1.8-7.7) years, 5-year OS rate was 86% (95% CI: 72-93) and 5-year DFS rate was 59% (95% CI: 43-71). Tumors recurred in 19 patients (13 lung, 3 liver and 7 others). Total 41 pts (79%) completed 12 courses of mFOLFOX6 (reasons for discontinuation: AEs in 3, refusal due to AEs in 8). AEs ( > Grade 3) were neutropenia 50%, fatigue 8%, peripheral sensory neuropathy 8%, appetite loss 4%, diarrhea 4%, febrile neutropenia 2% and allergic reaction 2%. There was no treatment related death. Conclusions: Adjuvant mFOLFOX6 is feasible and may be effective after metastasectomy for PM-CRC, considering much better OS than we had expected. Clinical trial information: UMIN000005693 .

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Carboplatin versus cisplatin-based adjuvant chemotherapy in elderly patients with stages IB, II, and IIIA non-small cell lung cancer in the community setting.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.7533 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 7533-7533 ◽

Cited By ~ 2

Author(s):

Fei Gu ◽

Juan P. Wisnivesky ◽

Grace Mhango ◽

Gary M. Strauss

Keyword(s):

Adjuvant Chemotherapy ◽

Cox Regression ◽

Community Setting ◽

Community Practice ◽

Propensity Score Methods ◽

Stage Ib ◽

Resected Stage ◽

Iiia Nsclc ◽

Nsclc Patients ◽

Medicare Database

7533 Background: It remains controversial whether completely resected elderly NSCLC patients should receive adjuvant chemotherapy (ACT) and with what treatment regimen. We previously reported from a SEER-Medicare analysis of cases diagnosed up to 2005, that carbo-ACT is given much more frequently than cis-ACT and both are associated with improved overall survival (OS). Since randomized ACT trials were published around 2005, an update is necessary to reflect more recent practice patterns. Methods: We identified 16,420 patients >65 years in the SEER-Medicare database with resected stage IB-IIIA NSCLC, diagnosed between 1992 and 2007. Among these patients, 1,803 (11%) received platinum-ACT. Propensity score methods and Cox regression analyses were used to assess survival outcomes, as well as to compare carbo- versus cis-based therapy, while controlling for potential confounders. Results: Among those receiving platinum-based ACT, of whom 83% received carbo, there was a significant OS survival advantage compared to those receiving no ACT (TABLE). Carbo-ACT is associated with similar OS as compared to cis-ACT. The carbo/paclitaxel doublet was the most commonly used regimen, given to 52%. Chemotherapy-related toxicities requiring hospitalization were comparable between carbo- and cis-ACT groups, except for significantly less dehydration and anemia among those receiving carbo-ACT. Conclusions: In community practice reflected in this SEER-Medicare study, a minority of completely resected stage IB-IIIA NSCLC received platinum-based ACT that is associated with improved OS. Carbo-ACT was given in a 5:1 ratio compared to cis-ACT, had comparable OS advantage, and a somewhat more favorable toxicity profile. [Table: see text]

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Phase II study of an oxaliplatin-based regimen for relapsed colon cancer patients treated with oxaliplatin-based adjuvant chemotherapy (INSPIRE study)

Cancer Chemotherapy and Pharmacology ◽

10.1007/s00280-021-04232-2 ◽

2021 ◽

Author(s):

Keiichiro Ishibashi ◽

Toru Aoyama ◽

Masahito Kotaka ◽

Hironaga Satake ◽

Yasushi Tsuji ◽

...

Keyword(s):

Colon Cancer ◽

Adjuvant Chemotherapy ◽

Cancer Patients ◽

Sensory Neuropathy ◽

Progression Free Survival ◽

First Line ◽

Secondary Endpoints ◽

Grade 3 ◽

Peripheral Sensory ◽

Line Chemotherapy

Abstract Background The aim of this study was to evaluate the efficacy and safety of first-line chemotherapy with re-introduction of oxaliplatin (OX) more than 6 months after adjuvant chemotherapy including OX. Methods Stage II/III colon cancer patients with neuropathies of grade ≤ 1 who relapsed more than 6 months after adjuvant chemotherapy including OX were considered eligible. Eligible patients were treated with 5-fluorouracil, l-leucovorin and OX plus molecularly targeted agents or capecitabine and OX plus bevacizumab (BV) or S-1 and OX plus BV. The primary endpoint was the progression-free survival (PFS), and the secondary endpoints were the overall survival (OS), response rate (RR) and toxicity. Results A total of 50 patients were enrolled between September 2013 and May 2019. Twelve patients received 5-fluorouracil, l-leucovorin and OX (FOLFOX) plus BV, 21 patients received capecitabine and OX plus BV, 10 patients received S-1 and OX plus BV and 7 patients received FOLFOX plus cetuximab or panitumumab. The median PFS was 11.5 months (95% confidence interval [CI] 8.3–16.0), the median OS was 45.4 months (95% CI 37.4–NA), and the RR was 56.0% (95% CI 42.3–68.8). Adverse events of grade ≥ 3 that occurred in ≥ 5% of cases were neutropenia in 6 patients (12%), peripheral sensory neuropathy in 5 patients (10%), diarrhea in 4 patients (8%), hypertension in 4 patients (8%), anorexia in 3 patients (6%) and allergic reactions in 3 patients (6%). Conclusions First-line chemotherapy with re-introduction of OX more than 6 months after adjuvant chemotherapy including OX can be used safely with expected efficacy for relapsed colon cancer patients.

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