Cycles Of Cap Research Articles

Adjuvant capecitabine versus nihil in older patients with node-positive/high-risk node-negative early breast cancer receiving ibandronate – The ICE randomized clinical trial

Aim of the studyEvaluation of the impact of a de-escaleted chemotherapy regimen consisting of capecitabine (Cap) on invasive disease-free survival (iDFS) in patients ≥65 years with node-positive/high-risk node-negative early breast cancer (BC) receiving ibandronate (Ib). MethodsICE (Ib with or without Cap in Elderly patients with early breast cancer) was a multicentre phase 3 clinical trial with a 2020 update of long-term follow-up for overall survival enroling node-positive/high-risk node-negative patients ≥65 years with early BC. Patients were randomised to Cap 2000 mg/m² day 1–14 q3w for 6 cycles plus Ib (50 mg p.o. daily or alternatively 6 mg intravenous q4w) or Ib alone for 2 years. Endocrine therapy was recommended for hormone receptor (HR)-positive patients. The primary endpoint was iDFS analysed using Cox proportional hazards regression and log-rank analysis. Results1358 (96.4%) of 1409 randomised patients started treatment. 564 (83.4%) completed 6 cycles of Cap. 513 (77.7%) and 516 (78.8%) completed Ib in the Cap+Ib and Ib alone arm, respectively. Median age was 71 (range 64–88) years, 1099 (81%) were HR-positive, 705 (51.9%) node-negative. At a median follow-up of 61.3 months, 5-year iDFS was 78.8% for Cap+Ib versus 75.0% for Ib alone (p = 0.80). Effects were independent of age, nodal, and HR status. The addition of Cap caused significantly higher skin and gastrointestinal toxicity. ConclusionsThe adjuvant combination of Cap+Ib did not show significantly better iDFS than Ib alone in node-positive/high-risk node-negative older BC patients, of whom HR-positive patients were also treated with endocrine therapy. Trial registrationStudy in elderly patients with early breast cancer (ICE), NCT 00196859, https://clinicaltrials.gov/ct2/show/NCT00196859?term=NCT00196859.

GYNECOLOGICAL MALIGNANCIES

A large study of tumors of low malignant potential confirmed the favorable survival in this group of patients compared to invasive epithelial ovarian tumors. Only 8% of patients died with recurrent disease after surgery. Patients with stage IA borderline tumors with mucinous histology tended to recur later and carried a poorer prognosis than patients with serous histology and similar stage. The group at highest risk for relapse were age greater than 70, stage II or III tumors, and histology other than serous. Long-term survival in this group was less than 75%. This high-risk group of patients should be targeted for innovative adjuvant treatment strategies. This year several well-designed studies with large sample sizes showed DNA ploidy to be an important new independent prognostic factor in stage I ovarian carcinoma. In patients with well-differentiated early stage ovarian cancer, DNA flow cytometric analysis may indicate subgroups with less favorable prognostic characteristics. This method of analysis may be beneficial in determining the need for additional treatments after surgery for early stage ovarian carcinoma. Recommendations for the definitive management of early stage ovarian cancer awaits completion of current GOG and European randomized prospective studies. Paclitaxel given in combination with platinum-containing agents is an intense area of research for treatment of advanced stage disease. Early data from a prospective randomized trial of patients with advanced ovarian cancer showed a higher response rate and longer disease-free survival in patients treated with paclitaxel and cisplatin compared to a standard regimen of cyclophosphamide and cisplatin. The impact of this treatment on long-term survival awaits maturation of data. Preliminary results evaluating G-CSF in combination with paclitaxel and cisplatin for dose escalation was reported. Paclitaxel, 250 mg/m2, and cisplatin, 75 mg/m2, were the maximally tolerated doses, with peripheral neuropathy or myalgias the dose limiting toxicities. Further studies are now underway to test the effect of dose-response with escalation therapies and to determine the optimal dose and schedule for the management of patients with advanced ovarian cancer. IL-3 significantly ameliorated neutropenia but did not prevent cumulative platelet toxicity in a regimen utilizing high-dose carboplatin. This mild improvement in myelosuppression was obtained at the cost of significant toxicity. Nausea, vomiting, malaise, bone pain, headache, fever, chills and facial flushing were frequent. Intraperitoneal chemotherapy was tested as a means of consolidation treatment for patients after having a negative second-look laparotomy. These treatments were shown to be feasible; however, prospective randomized trials will be necessary to determine a benefit over operative therapy alone. Several studies addressed to problem of residual disease after primary surgery and adjuvant chemotherapy. A large phase II study conducted by the GOG confirmed the activity of salvage cisplatin-based intraperitoneal chemotherapy in patients with small-volume residual ovarian cancer with favorable pretreatment characteristics. Whether intraperitoneal platinum-based therapy represents an advantage over systemic platinum therapy is being addressed in a prospective SWOG study. The use of six additional cycles of CAP for treatment of residual disease after primary treatment of surgery and adjuvant chemotherapy did not significantly improve complete pathological response and survival. Prolonged duration of chemotherapy above six cycles is not likely to impact treatment for residual disease. A regimen of high dose carboplatin was compared to whole abdominal radiotherapy for treatment of residual disease after initial chemotherapy. There was no difference in survival or disease-free survival between treatments.(ABSTRACT TRUNCATED)

Neoadjuvant Treatment of Stage IIB/III Triple Negative Breast Cancer with Cyclophosphamide, Doxorubicin, and Cisplatin (CAP Regimen): A Single Arm, Single Center Phase II Study (GBECAM 2008/02).

The DNA damaging platinum salts have been explored in the treatment of triple negative breast cancer (TNBC) based on preclinical, and, more recently, clinical evidence of specific susceptibility of TNBC to these agents. Despite the increased toxicity, treatment intensification with polychemotherapy improves response and might be of interest in patients presenting with large primaries. In this trial, we aimed at exploring the efficacy and tolerability of the addition of cisplatin to standard anthracycline-cyclophosphamide backbone in patients with stage IIB/III TNBC. This is a single arm, single center, non-randomized, phase II trial of stage IIB/III TNBC. Patients received neoadjuvant chemotherapy with cisplatin (50 mg/m2) in combination with doxorubicin (50 mg/m2) and cyclophosphamide (500 mg/m2) every 21 days and for a total of six cycles (CAP). After surgery, adjuvant chemotherapy consisting of docetaxel (75 mg/m2) every 21 days was further provided for four cycles. Primary outcome was pathological complete response in the breast and axilla (pCR; ypT0ypN0). Secondary outcomes were safety, disease-free survival (DFS), and overall survival (OS). Eight (19.5%) out of 41 patients reached a pCR and 35 (85.4%) had a clinical complete or partial response. After a median follow-up of 47.4 months (interquartile range 30.9-61.9), the proportion of patients free of recurrence or death at 3 years was of 51.8% [95% confidence interval (CI) 34.6-66.5%], while the proportion of patients alive at 3 years was of 55.5% (95% CI 37.8-70.1%). Patients with a pCR rate or family history of breast and/or ovarian cancer showed a numerical but statistically non-significant trend for improved DFS and OS. The majority of patients received six cycles of CAP (82.9%). The three most common grade ≥3 adverse events were nausea (16.3%), vomiting (14.0%), and neutropenia (9.3%). Febrile neutropenia occurred in three patients (7.0%). Cisplatin in association with doxorubicin and cyclophosphamide was associated with a pCR rate of 19.5% in a cohort of patients with predominantly stage III tumors. The tolerability profile of this combination poses clinical challenges to its general use in clinical practice. GBECAM 2008/02. NCT03304756.

Abstract OT3-1-06: CIBOMA/2004-01_GEICAM/2003-11: A randomised phase III trial assessing adjuvant capecitabine (Cap) maintenance therapy after standard chemotherapy for triple-negative early breast cancer (EBC)

Abstract Background: The ideal adjuvant treatment of triple negative EBC remains to be defined. CIBOMA/2004-01_GEICAM/2003-11 is a multinational randomized phase III trial exploring adjuvant Cap after the conclusion of conventional chemotherapy in triple-negative EBC patients. Materials and Methods: Patients with operable, node-positive (or node-negative with tumour diameter ≥1 cm), hormone receptor-negative, HER2-negative EBC that have received 6–8 cycles of standard anthracycline and/or taxane-containing chemotherapy in the (neo)adjuvant setting (doxorubicin–cyclophosphamide x 4 allowed for node-negative disease), followed by radiotherapy (if indicated) are eligible. After central confirmation of triple negativity by immunohistochemistry, patients were randomised to either 8 cycles of Cap (1,000 mg/m2 bid, d1–14 q21d) or observation. Stratification factors: centre, prior taxane (yes vs. no), involved nodes (0 vs. 1–3 vs. ≥4) and phenotype (basal vs. non-basal). The primary endpoint is disease-free survival (DFS). Secondary endpoints include 5-year DFS, overall survival and safety. An optional pharmacogenetic sub-study will explore polymorphisms of thymidylate synthase and methylenetetrahydrofolate reductase in relation to efficacy and tolerability of Cap. Present Status: Recruitment of 876 randomized patients was completed in September 2011. Statistical assumptions: expected 30% reduction in the risk of recurrence at 5 years (64.7% to 73.7%, HR 0.701), power of 80% and 0.05 two-sided significance level. Final efficacy analysis will be triggered by 255 events. Baseline characteristics are well balanced and shown in the table below. 75.0% of the patients completed the 8 cycles of adjuvant Cap. Baseline patients characteristics Capecitabine (n = 448)Observation (n = 428)Median Age, years (range)51 (20-79)50 (24-83)Basal Phenotype,%70.772.2Histology,% Ductal87.786.1Lobular1.82.3Other9.811.4Unknown0.70.2Grade,% 13.32.8218.119.0371.969.6Not determinable6.08.4Unknown0.70.2Chemotherapy received,% Adjuvant (only)78.982.2Neoadjuvant (only)15.615.0Adjuvant + Neoadjuvant4.22.6Unknown1.30.2Postmenopausal,%69.267.3Prior Chemotherapy Agents,% Anthracyclines without taxanes32.132.2Anthracyclines and taxanes67.267.6Unknown0.70.2 Conclusions: This randomized phase III adjuvant trial in triple negative EBC patients has completed accrual and event follow up is ongoing. The trial is sponsored by CIBOMA/GEICAM. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr OT3-1-06.

1161P - Treatment of Advanced Neuroendocrine Tumours: Final Results of the Ukinets and Ncri Randomised Phase 2 Net01 Trial

ABSTRACT Background Chemotherapy is widely used for advanced, unresectable neuroendocine tumours (NETs) but only four randomised trials are published. The first combined streptozocin (strep) and 5fluorouracil (5FU), reporting 63% response rate (RR), but subsequent retrospective studies had lower RRs (6-45%). Cisplatin has been combined with strep + 5FU in a retrospective study with promising activity in NETs and capecitabine (cap) has been effectively substituted for 5FU in many tumours. The NET01 trial was designed to investigate whether cap + strep ± cisplatin warrant further evaluation. Methods Patients (pts) with histologically confirmed, unresectable, advanced and/or metastatic NETs of foregut, pancreatic or unknown primary site were randomised (1:1) to 6 cycles of 3-weekly cap 625 mg/m2 po bd daily (D1-21), strep 1.0g/m2 IV (D1), with cisplatin 70mg/m2 IV (D1) (Cap-strep-cist) or without (Cap-strep). The primary outcome measure was RR using RECIST criteria. 84 pts were required to test a RR of 60% with a significance level of 5% and 80% power in each arm. Central pathology review and 10% of central radiology review were performed. Results 86 pts (58% male, median age 59 years) were randomised (44 Cap-strep, 42 Cap-strep-cist) with primary site – foregut 20%, pancreatic 48% and unknown 33%. The grade was low 12 (17%), intermediate 43 (62%) and high 14 (20%). Baseline characteristics were balanced between the 2 arms. 59% Cap-strep and 33% Cap-strep-cist pts received ≥6 cycles. 18 Cap-strep and 26 Cap-strep-cist pts experienced grade ≥3 toxicities. Outcome results are summarised in the table. Cap-strep-cist Cap-strep Response PR SD PD n = 38 13% 61% 26% n = 40 8% 73% 20% PFS No. progressions/deaths, n(%) Median (mo) n = 42 35 (83%) 9.7 n = 44 34 (77%) 10.2 OS No. deaths, n(%) Median (mo) n = 42 22 (52%) 27.5 n = 44 25 (57%) 26.7 Conclusions The novel Cap-strep ± cisplatin regimens were associated with overall disease control and survival durations consistent with published studies. Cap-strep was better tolerated than Cap-strep-cist. Further prospective randomised trials are needed to determine optimal NET chemotherapy. Disclosure D. Cunningham: Research Funding: Amgen, Roche. Astra Zeneca Expert testimony: Amgen (Uncompensated) Honoraria: None Advisory: Amgen Roche (Uncompensated). All other authors have declared no conflicts of interest.

Treatment of advanced neuroendocrine tumors: Results of the UKINETS and NCRI randomized phase II NET01 trial.

4121 Background: Chemotherapy is widely used for advanced, unresectable neuroendocine tumours (NETs) but only four randomised trials are published. The first combined streptozocin (strep) and 5fluorouracil (5FU), reporting 63% response rate (RR), but subsequent retrospective studies had lower RRs (6-45%). Cisplatin has been combined with strep+5FU in a retrospective study with promising activity in NETs and capecitabine (cap) has been effectively substituted for 5FU in many tumours. The NET01 trial was designed to investigate whether cap+strep ± cisplatin warrant further evaluation. Methods: Patients (pts) with histologically confirmed, unresectable, advanced and/or metastatic NETs of foregut, pancreatic or unknown primary site were randomised (ratio 1:1) to 6 cycles of 3-weekly cap 625 mg/m2 po bd daily (D1-21), strep 1.0g/m2 IV (D1), with cisplatin 70mg/m2 IV(D1) (Cap-cist) or without (Cap-strep). The primary outcome measure was RR using RECIST criteria (v 1.0). 84 pts were required to test a RR of <40% vs >60% with a significance level of 5% and 80% power in each arm. Central pathology review was performed; retrospective central radiology review was undertaken on 10% of randomly selected cases. Results: 86 pts (58% male, median age 59 years) were randomised (44 Cap-strep, 42 Cap-cist) with primary site – foregut 20%, pancreatic 48% and unknown 33%. The grade was low 8 (11%), intermediate 47 (67%) and high 15 (21%). Baseline characteristics were balanced between the 2 arms. 60% Cap-strep pts received ≥6 cycles compared with 33% Cap-cist pts. 17 Cap-strep and 26 Cap-cist pts experienced grade ≥3 toxicities. Outcome results are summarised in the table. Ki67, mitotic index or primary site of origin did not appear to predict for response. Conclusions: The novel Cap-strep ± cisplatin regimens were associated with overall disease control and survival durations consistent with published studies. Cap-strep was better tolerated than Cap-cist. Further prospective randomised studies are required to determine optimal NET chemotherapy. [Table: see text]

Comparison of magnetic resonance imaging and histopathological response to neoadjuvant chemotherapy in locally advanced rectal cancer: The GEMCAD 0801 trial.

e14097 Background: MRI methods for rectal cancer response assessment post chemoradiotherapy include post treatment T staging(ymrT), tumor regression grading(mrTRG) and length change/modified RECIST measurement. The usefulness of MRI in evaluating response to neoadjuvant chemotherapy has not been investigated. We assessed the reproducibility and agreement of these three parameters with histopathological T and TRG stage(ypT, pTRG). Methods: 28 eligible patients were enrolled in a prospective phase II trial to evaluate safety and efficacy of neoadjuvant CAPOX-B in patients with MRI defined T3 rectal adenocarcinoma. Patients received 4 cycles of Cap 2000 mg/m2(d1-14),Ox 130 mg/m2(d1) and B 7.5 mg/kg(d1) every 3 weeks(last cycle without B). Seven radiologists assessed MRIs using the following categories: ymrT (T0-T4 using T3 substaging), mrTRG (1-5), and length change(Stable disease, Complete response,Partial response). Agreement was assessed by kappa (central reviewer data verses each local centre reviewer).Agreement between central reviewer MRI results and both pathology endpoints was also assessed. Results: 24 patients had evaluable pre and post chemotherapy imaging and pathology (4 did not have post treatment MRI). Thirteen patients had good response (ypT0-3a) and 11 had poor response (>ypT3a). Sixteen patients had good pTRG(2-4) and 8 had poor pTRG(0&1). ymrTRG showed a moderate level of reproducibility;K=0.45-0.58. ymrT showed a fair to moderate level of agreement;K=0.2-0.53. Length assessment also showed a fair level of agreement; K=0.21-0.38. ymrTRG showed 75% agreement with ypT(16/22); K=0.49(0.13-0.84) and 79% agreement with pTRG(19/24); K=0.55(0.22-0.88). ymrT showed a fair level of agreement with ypT;K=0.21, pTRG;K=0.2, length assessment showed slight agreement with ypT;K=0.1, pTRG;K=0.1. Conclusions: This is the first study to show MRI can evaluate response of rectal cancer following neoadjuvant chemotherapy. As mrTRG showed best agreement with pathology, we recommend mrTRG as the preferred method of post treatment assessment in this setting.

Neoadjuvant capecitabine, oxliplatin, and bevacizumab (CAPOX-B) in intermediate-risk rectal cancer (RC) patients defined by magnetic resonance (MR): GEMCAD 0801 trial.

3586 Background: Retrospective data suggest that RT might not be needed in all patients with stage II/III RC. Modern systemic therapy might have local efficacy similar to chemoradiation (CRT). Methods: A multicenter phase II trial was undertaken to evaluate safety and efficacy of neoadjuvant CAPOX-B in patients with T3 middle third rectal adenocarcinoma. Eligible patients (pts) had measurable disease at the baseline and candidate for R0 total mesorectal escision (TME) with intermediate-risk defined by pelvic MR a) T3 with distal border of tumor > 5 cm from the anal verge and below the sacral promontory. b) tumor ≥2 mm from the mesorectal fascia. Pts received 4 cycles of Cap 2000 mg/m2 (d1-14), Ox 130 mg/m2 (d1) and B 7.5 mg/kg (d1) every 3 weeks (last cycle without B). Pts undergo re-staging with MR. One radiologist reviewed all pre- and post-treatment MR scans independently. Pts without progression proceed to TME 4-6 weeks from the last cycle. If progression, pts were to be referred for pre-op cap/RT followed by TME. 1º Endpoint: Tumor Response (RECIST). Design: Simon 2-stage; 28 pts 1st stage and 46 pts 2nd stage. We report data on the planned analysis of pts included for 1st stage. Results: 28 eligible pts (10F/18M) were enrolled from 7/09-5/11. Tumor response, compliance and toxicity details are shown in table below. Two pN2 pts received postop Cap/RT. Conclusions: Neoadjuvant CAPOX-B is active and safe. Early parameters of efficacy are encouraging and seem similar to those observed with CRT. [Table: see text]

Multicenter randomized phase II study of chemoradiation (CRT) followed by surgery (S) and chemotherapy (CT) versus induction CT followed by CRT and S in high-risk rectal cancer: GCR-3 final efficacy and safety results

4103 Background: In locally advanced RC the optimal therapeutic sequence remains an important clinical question. Induction CT prior to CRT and S may be associated with better efficacy and compliance. Methods: Eligible pts had medium or distal high risk RC defined by MRI and/or US: Tumors within 2mm of mesorectal fascia, distal T3 at/below levators, resectable T4 and T3N+. Pts, stratified by center, were randomized assigned to receive either Arm A : capecitabine (Cap) 825 mg/m2 BID 5 d/w, oxaliplatin (Ox) 50 mg/m2 IV weekly x 5 and concomitant RT: 50.4 Gy in 28 fractions. S was planned 5–6 w after CRT. Post-op four cycles of Cap 1,000 mg/m2 bid days 1 to 14; Ox 130 mg/m2 day 1 or Arm B: Induction CapOx followed by CRT and S. Two parallel, Simon 2-stage designs: α=0.05 β=0.1; 24 evaluable pts/arm 1st stage and 54 pts/arm for 2nd stage. Primary endpoint: pathological complete response (pCR). Secondary endpoints included toxicity and treatment compliance. Results: 108 Pts were randomly assigned (arm A/B, 52/56), and 103 were assessable (49/54) from 14 sites. Median age 62/60 years, Male 65/70%. During treatment period 6 pts died A/B: 2 vascular, 1 suicide/ 3 post-op. Pts with any grade ¾ toxicity during CRT were arm A/B: 29% (14/49) and 23% (12/53). Any grade ¾ toxicity during adjuvant/induction CT were 51% (19/37) and 17% (9/54); χ2,p= 0.0004. On an intent-to-treat basis the pCR for Arm A/B was achieved in seven (13.5%; 95% CI, 5.6%-25.8%) and eight (14.3%; 95% CI, 6.4%-26.2%). R0 resections were achieved in 92% (45/49) and 88% (48/54). 51% (25/49) and 93% (50/54) received all four cycles of adjuvant/induction CT (χ2;p<0.0001). Relative Median Dose intensity of adjuvant /induction CT was 0.74/0.96 (Wilcoxon; p<0.0001) for Cap and 0.75/1.0 (Wilcoxon; p<0.0001) for Ox. Conclusions: Induction CT prior to CRT has more favorable compliance and toxicity profiles. Furthermore, there is no compromise in pCR and R0 resection rates. Larger trials evaluating this strategy are justified. [Table: see text]

International randomized phase III study of capecitabine (Cap), bevacizumab (Bev), and mitomycin C (MMC) in first-line metastatic colorectal cancer (mCRC): Final results of the AGITG MAX trial

4023 Background: The addition of Bev to oxaliplatin or irinotecan based doublet chemotherapy has shown benefit in mCRC. Cap± MMC are alternate chemotherapy regimens suitable for patients (pts) who are either unfit for or who do not require initial oxaliplatin/irinotecan. This phase III study compared Cap with Cap Bev and Cap Bev MMC. The aim was to develop a low toxicity regimen suitable for a broad population of pts with mCRC. Methods: Previously untreated pts with unresectable mCRC considered suitable for Cap monotherapy were randomised to arm A Cap (Cap 2000mg/m2/d or 2500mg/m2 d1–14 q21d), arm B Cap Bev (Bev 7.5mg/kg q3w) or arm C Cap Bev MMC (MMC 7mg/m2 q6w). Primary endpoint: PFS, secondary endpoints: RR, toxicity, OS, QoL . Randomisation was stratified by age, PS, centre and Cap dose. Response was assessed every 6w. The study was designed to detect an increase in the median PFS from 5.5m (arm A) to 8m (arm B or C) at p<0.025 with 80% power. Results: A total of 471 pts were randomised from July 2005-June 2007. Outcomes were evaluated on an intention to treat basis and included 15 ineligible pts. Baseline demographics were well balanced between arms with median age 67y (range 31–86y). Toxicity was reported: ASCO 2008 abstr 4029. The most common grade 3/4 toxicities were PPE (16%, 26%, 28%) and diarrhoea (11%, 17%, 16%) for arms (A,B,C). However, adjusted rates per cycle were similar as arms B & C received more cycles of Cap (A8.3, B10.8, C10.5). Other toxicity rates were generally <10%. The study achieved its primary endpoint with a highly significant improvement in PFS for arms B & C. RR and OS are summarized ( Table ). Conclusions: All treatment regimens were well tolerated in a relatively elderly patient cohort. The addition of Bev±MMC to Cap significantly improved PFS without significant additional toxicity. OS was similar for all arms. Cap Bev±MMC is an active, low toxicity regimen that may be considered as a treatment option for pts with mCRC. [Table: see text] [Table: see text]

Oral Capecitabine in Gemcitabine-Pretreated Patients with Advanced Pancreatic Cancer

Objective: To date, no standard regimen for salvage chemotherapy after gemcitabine (Gem) failure has been defined for patients with advanced pancreatic cancer (PC). Oral capecitabine (Cap) has shown promising activity in first-line chemotherapy trials in PC patients. Methods: Within a prospective single-center study, Cap was offered to patients who had already received at least 1 previous treatment regimen containing full-dose Gem (as a single agent, as part of a combination chemotherapy regimen or sequentially within a chemoradiotherapy protocol). Cap was administered orally at a dose of 1,250 mg/m² twice daily for 14 days followed by 7 days of rest. Study endpoints were objective tumor response rate by imaging criteria (according to RECIST), carbohydrate antigen 19-9 (CA19-9) tumor marker response, time to progression, overall survival and toxicity. Results: A median of 3 treatment cycles (range 1–36) was given to 39 patients. After a median follow-up of 6.6 months, 27 patients were evaluable for response: no complete or partial responses were observed, but 15 patients (39%) had stable disease. A CA19-9 reduction of >20% after 2 cycles of Cap was documented in 6 patients (15%). Median time to progression was 2.3 months (range 0.5–45.1) and median overall survival (since start of Cap treatment) was 7.6 months (range 0.7–45.1). Predominant grade 2 and 3 toxicities (per patient analysis) were hand-foot syndrome 28% (13% grade 3); anemia 23%; leg edema 15%; diarrhea 13%; nausea/vomiting 10%, and leukocytopenia 10%. Conclusion: Single-agent Cap is a safe treatment option for Gem-pretreated patients with advanced PC. Further evaluation of Cap in controlled clinical trials of Gem-pretreated patients with advanced PC is recommended.

A Prospective Randomized Comparison of 6 and 12 Cycles of Cyclophosphamide, Adriamycin, and Cisplatin in Advanced Epithelial Ovarian Cancer: A Danish Ovarian Study Group Trial (DACOVA)

Two hundred-two patients with FIGO stages III and IV epithelial ovarian cancer were randomized to 6 or 12 cycles of cyclophosphamide, Adriamycin, and cisplatin (CAP). Patients in complete clinical response underwent a second-look laparotomy, 1 month after cessation of chemotherapy. Patients randomized to 6 cycles and found to be in partial remission at second-look were to receive a further 6 cycles of CAP. Rate of complete pathological response was 23% for 6 cycles of CAP and 25% for 12 cycles; the median survival was 23 months for 6 cycles and 27 months for 12 cycles, and 3-year survival was 29% for 6 cycles and 35% for 12 cycles. None of these differences were statistically significant. Fifty-four patients randomized to 6 cycles were found to be in partial surgical remission at second-look laparotomy, and 24 of these patients agreed to a further 6 cycles and a third-look laparotomy. Six of these 24 patients had a complete pathological response at third-look, improving the complete response rate to 28% in those originally randomized to 6 cycles. However, 3 of these patients all had macroscopic tumors removed at second-look, and two had microscopic disease at second-look. Among patients achieving complete response mean cumulative doses in the CAP 6 cycle group were approximately 50% of those in the CAP 12 cycle group. However, when all patients were considered, this difference was only approximately 15% owing the continuation of chemotherapy in the partial responders of the 6 cycle group and early stopping for chemotherapy in the CAP 12 cycle group due to toxicity or progression. Patients in complete pathological response also showed similar survivals for 6 and 12 cycles. In conclusion, the study did not show a correlation between mean cumulative doses and complete pathological response and survival.

Randomized prospective trial of 5 versus 10 cycles of cyclophosphamide, doxorubicin, and cisplatin in advanced ovarian carcinoma

Five versus ten cycles of cyclophosphamide, doxorubicin, and cisplatin (CAP) were compared in advanced ovarian carcinoma by a prospective randomized study of 78 patients, 41 receiving 5 cycles (CAPS) and 37 receiving 10 cycles (CAP10) of chemotherapy. Patients were stratified by histologic grade and size of residual disease. Cyclophosphamide, 600 mg/m 2, doxorubicin, 40 mg/m 2, and cisplatin, 100 mg/m 2, were administered every 4 weeks for 5 or 10 cycles. Second-look laparotomy was performed to evaluate response and plan further therapy. CAPS patients found at second-look laparotomy to have partially responded to chemotherapy were treated with 5 additional cycles of CAP. CAP10 was more toxic than CAPS with respect to myelosuppression, hospital admissions for nadir fever, median elevation of creatinine, and degree of peripheral neuropathy. Median follow-up is 64 months. CAPS and CAP10 were equivalent in surgically documented complete responses (34 versus 35%) and survival ( P = 0.41). Twelve partial responders to CAPS received additional CAP chemotherapy; one complete response resulted. We conclude that CAP5 is preferable to CAP10 in treatment of advanced ovarian cancer as it is equally effective and less toxic.

Cyclophosphamide, adriamycin, and cis-platinum (CAP) in metastatic and locally advanced breast cancer.

A combination of cyclophosphamide, adriamycin, and cis-platinum (CAP) was tested in 20 previously untreated patients with locally advanced or metastatic breast cancer with the aim of assessing the ability of this platinum-containing regimen to induce a high complete remission rate. The drug regimen was given on a 3/week schedule at the following doses: cyclophosphamide 200 mg/m2 i.v. on days 1, 2, 3; adriamycin 40 mg/m2 i.v. or day 1 and cis-platinum 20 mg/m2 i.v. plus hydration on days 1, 2, 3. In the absence of progression, six cycles of CAP were planned and response was evaluated at that time. Thirteen of 20 patients achieved partial remission (65%) but only one obtained complete remission (5%). Overall median duration of response was 9 months (range 4-20 + months). Tumor response was mainly documented in soft tissues (primary tumor: 14 of 16; other sites: 19 of 20). Grade II leukopenia was documented in 60% of patients. All patients experienced moderate to severe gastrointestinal toxicity and alopecia was universal. No renal toxicity was observed. Although CAP regimen at the given dose schedule induced a high overall response rate (70%), the complete remission rate in this limited number of patients was lower than expected. These results do not appear superior to those achieved with conventional drug regimens.

Inoperable non-small cell lung cancer: Radiation with or without chemotherapy

We report a randomized multicentre study of split-course radiotherapy (RT), with or without combination chemotherapy (CT), in 238 patients with inoperable non-small cell lung cancer (NSCLC), previously untreated, confined to one hemithorax and the mediastinal nodes. In both treatment groups RT consisted of 55 Gy in 20 F given over 7 weeks wih a 3-week rest interval. CT consisted of the 3-drug regimen CAP: C = cyclophosphamide 400 mg/m 2 , A = adriamycin 40 mg/m 2 , P = cisplatin 40 mg/m 2 ; 2 cycles of CAP given before RT, one during the rest interval and six after RT. Seventy per cent in the RT arm and 67% in the RT-CT arm had epidermoid carcinoma. No significant difference was apparent between the RT and the RT-CT arms with respect to objective response rates (CR + PR) ( 44 and 49%, respectively), median duration of response ( 278 and 320 days), local failure ( 31 and 20%), distant progression ( 23 and 20%) or median survival ( 311 and 322 days). The survival figures showed an almost significant (P = 0.05) therapeutic advantage of the combined regimen with stage IIIM 0 disease. Progressive disease was the cause of death in 92% and 88%. We conclude that chemotherapy did not contribute significantly to either local control or survival as compared to radiotherapy alone.

Cyclophosphamide, doxorubicin, and cisplatin combination chemotherapy for advanced carcinomas of salivary gland origin.

Thirteen patients with carcinomas of major and minor salivary gland origin (nine adenoid cystic carcinomas and four adenocarcinomas) were treated with cyclophosphamide (500 mg/m2), doxorubicin (50 mg/m2), and cisplatin (50 mg/m2) (CAP) by intravenous injections on the first day of a 28-day regimen. Sixty-one cycles of CAP were administered (mean, 4.7 cycles per patient). Eleven patients were treated for palliation of recurrent disease (locoregional, ten; lung, ten; liver, three; and bone, three). Two patients untreated previously, one with extensive local disease involving the base of the skull and one with a solitary lung metastasis (resected with a positive margin) and an initially unappreciated base of tongue primary, received two cycles of CAP followed by local treatment and adjuvant CAP. Previous therapy for the 11 patients with recurrent disease included surgery (ten), radiotherapy [RT(11)], chemotherapy (three), or hormonal therapy (two). Three complete and three partial responses to chemotherapy were noted for an overall response rate of 46%. The median duration of response in palliative patients was 5 months (range, 2 to 9). Of the two patients receiving induction CAP, one relapsed with distant disease 26 months after treatment, and the other remains disease-free after 60 months of follow-up examination. Chemotherapy was well tolerated generally, and no chemotherapy-related deaths occurred. One hypertensive patient suffered a stroke after 3 cycles of therapy. CAP is an active regimen against salivary gland carcinomas and deserves further study. Also, it may be of value as induction or adjuvant treatment for patients with advanced disease untreated previously.

Combination chemotherapy followed by radiation therapy in patients with regional stage III unresectable non-small cell lung cancer

A chemotherapy combination of cyclophosphamide, doxorubicin, and cisplatin (CAP) was administered to 30 patients with stage III M0 or M1 (supraclavicular nodes) unresectable non-small cell lung cancer before and after radiotherapy. All patients had mediastinal metastases and most had T2 or T3 primary lesions. The response rate (complete plus partial) after two cycles of CAP was 47%, which increased to 66% (24% complete response rate) following radiotherapy. The overall median survival from initiation of chemotherapy was 9 months. CNS relapse occurred in five (26%) of 19 responding patients who did not receive prophylactic cranial irradiation in the early part of the study.