Escalating dose of continuous infusion combination chemotherapy for refractory neuroblastoma.

1993 ◽  
Vol 11 (4) ◽  
pp. 623-629 ◽  
Author(s):  
L A Campbell ◽  
R C Seeger ◽  
R E Harris ◽  
J G Villablanca ◽  
K K Matthay
Keyword(s):  
Bone Marrow ◽  
Continuous Infusion ◽  
Poor Prognosis ◽  
Dose Intensity ◽  
Complete Response ◽  
Hematologic Toxicity ◽  
Heavily Pretreated ◽  
Pretreated Patients ◽  
Prognosis Group ◽  
Dose Levels

PURPOSE This trial was undertaken to determine if a continuous infusion format with increased dose-intensity had antitumor activity with tolerable toxicity in patients with advanced neuroblastoma. PATIENTS AND METHODS Forty heavily pretreated patients with refractory or progressive neuroblastoma received continuous infusion doxorubicin, cisplatin, and etoposide along with bolus ifosfamide in a dose-escalation format. A total of 79 courses of chemotherapy were administered at five different dose levels. RESULTS Fifteen of 35 assessable patients (43%) achieved either a partial response (PR) or complete response (CR), including five patients with a CR, three with a very good PR (VGPR), and seven with a PR. Hematologic toxicity was severe, but reversible, and other toxicities, although significant, were tolerable and much less than that accepted in a bone marrow transplantation (BMT) setting. CONCLUSION This investigation illustrates that response is possible even in an extremely poor-prognosis group of patients, and it suggests that such a regimen may be effective if given before disease progression occurs.

Topotecan in heavily pretreated patients with recurrent ovarian, peritoneal, and fallopian tube carcinoma

2005 ◽  
Vol 15 (4) ◽  
pp. 612-617 ◽  
Author(s):  
B. Piura ◽  
A. Rabinovich
Keyword(s):  
Partial Response ◽  
Fallopian Tube ◽  
Dose Intensity ◽  
Complete Response ◽  
Ca 125 ◽  
Hematologic Toxicity ◽  
Fallopian Tube Carcinoma ◽  
Heavily Pretreated ◽  
Pretreated Patients ◽  
Grade 3

Topotecan has demonstrated antitumor activity in heavily pretreated patients with ovarian carcinoma. This report examines the activity and toxicity of topotecan in 29 heavily pretreated patients with recurrent ovarian, peritoneal, and fallopian tube carcinoma. Topotecan 1.5 mg/m2 was administered intravenously on days 1–5, every 21 days. It was second-line chemotherapy in 6 (20.7%) patients, third-line in 15 (51.7%), fourth-line in 4 (13.8%), fifth-line in 3 (10.3%), and seventh-line in 1 (3.4%). Median dose intensity was 1.667 mg/m2/week, and median relative dose intensity was 0.67. Disease complete response was observed in 5 (17.2%) patients, partial response in 1 (3.4%), stable disease in 12 (41.4%), and progressive disease in 11 (37.9%). CA-125 complete response was observed in 3 (10.3%) patients, partial response in 11 (37.9%), stable level in 5 (17.2%), and progressive level in 9 (31%), and no data were available in 1 (3.4%) patient. Toxicity was mainly hematologic: grade 3–4 neutropenia was observed in 20 (69%) patients, grade 3–4 leukopenia in 12 (41.4%), grade 3–4 thrombocytopenia in 9 (31%), and grade 3–4 anemia in 2 (6.9%). It is concluded that topotecan has considerable activity and noncumulative hematologic toxicity in heavily pretreated patients with recurrent ovarian, peritoneal, and fallopian tube carcinoma.

Hydroxyurea, fluorouracil, and concomitant radiotherapy in poor-prognosis head and neck cancer: a phase I-II study.

1989 ◽  
Vol 7 (6) ◽  
pp. 761-768 ◽  
Author(s):  
E E Vokes ◽  
W R Panje ◽  
R L Schilsky ◽  
R Mick ◽  
A M Awan ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Head And Neck ◽  
Neck Cancer ◽  
Poor Prognosis ◽  
Local Therapy ◽  
Complete Response ◽  
Synergistic Activity ◽  
Dose Levels ◽  
Concomitant Radiotherapy

Hydroxyurea and fluorouracil (5-FU) are active cytotoxic drugs in head and neck cancer and have shown synergistic activity in vitro. Both drugs also act as radiosensitizers. Therefore, we administered radiotherapy at daily fractions of 180 to 200 cGy with simultaneous continuous infusion 5-FU at 800 mg/m2/d and escalating daily doses of hydroxyurea for five days. Cycles were repeated every other week until completion of radiotherapy. Thirty-nine inoperable patients were treated at six dose levels of hydroxyurea ranging from 500 mg to 3,000 mg orally daily. Little effect of hydroxyurea on the WBC or platelet count was noted in patients receiving less than 2,000 mg daily, whereas both parameters decreased progressively in patients receiving 2,000 mg daily or more. Mucositis occurred at all dose levels, requiring frequent dose reduction of 5-FU; however, in patients receiving a daily hydroxyurea dose of 2,000 mg or less, the median weekly 5-FU dose administered was 1,725 mg/m2 (86% of the intended 5-FU dose), whereas at daily hydroxyurea doses exceeding 2,000 mg, the median weekly 5-FU dose decreased to 1,133 mg/m2 (57%) (P = .001). Of 15 evaluable patients with recurrent disease after prior local therapy only one failed to respond; six had a complete response (CR), and eight a partial response (PR). Of 17 evaluable patients without prior local therapy, 12 had a CR, with no patient developing recurrence in the irradiated field to date; five patients had a PR. We conclude that the recommended dose of hydroxyurea in this regimen is 2,000 mg daily. That dose will cause mild to moderate myelosuppression and will allow for delivery of greater than 80% of the intended 5-FU dose. The activity of this regimen in poor-prognosis head and neck cancer exceeds 90%; its further investigation in previously untreated patients is warranted.

scholarly journals Pomalidomide-Dexamethasone in the Management of Heavily Pretreated Multiple Myeloma

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 1-1
Author(s):  
Claudio Cerchione ◽  
Lucio Catalano ◽  
Davide Nappi ◽  
Anna Emanuele Pareto ◽  
Gerardo Musuraca ◽  
...  
Keyword(s):  
Oral Administration ◽  
Oral Treatment ◽  
Novel Agents ◽  
Hematologic Toxicity ◽  
Salvage Regimen ◽  
Good Compliance ◽  
Impressive Result ◽  
Heavily Pretreated ◽  
Pretreated Patients ◽  
Grade 3

Background Pomalidomide is a new generation IMID, with a very good compliance, thanks to oral administration, which can be used also in heavily pretreated patients, in a domestic setting. Aims In this retrospective observational trial, It has been evaluated efficacy and tolerance of pomalidomide plus dexamethasone (PD) as salvage regimen in heavily pretreated patients with relapsed and refractory MM (rrMM), whose prognosis is particularly severe. Methods 57 patients (31 M/26 F), with rrMM, median age at diagnosis 69 years (r. 52-86), and median age at start of treatment 76 years (r.56-90) treated with several lines of treatments (median 7, r. 2-11), every refractory to all the drugs previously received (also Bortezomib, Thalidomide and Lenalidomide), received Pomalidomide-Dexamethasone (Pomalidomide 4 mg for 21 days, Dexamethasone 40 mg days 1,8,15,22, pegfilgrastim day +8) every 28 days, until progression. ISS was equally distributed, and cytogenetic at relapse was evaluable in 14 patients. All the patients had previously been treated with schedule containing bortezomib and IMIDs. 63% (36/57) had undergone at least to a single ASCT. All patients were relapsed and refractory to last therapies received before PD. Results Pomalidomide was well tolerated, with grade 3-4 transfusion-dependent anemia in 58% (33/57) of patients, 44% (23/57) grade 3-4 neutropenia (pegfilgrastim in primary prophylaxis was given, no hospitalization was required, no septic shocks were observed), 40% (23/57) grade 3-4 thrombocytopenia without hemorrhagic events and transfusion-dependence. No severe extra-hematologic toxicity was observed. According to IMWG, ORR1 (≥PR) was 47.3% (27/57: 5 CR, 11 VGPR, 7 PR, 4 MR), but, considering that we are evaluating a cohort of heavily pretreated patients, with poor prognosis, another parameter should be considered, ORR2 (≥SD), considering stable disease as a successful result in progressive MM. ORR2 was 77.1% (17 SD). These can be considered as impressive result in this subset of patients. Oral treatment gives a really good compliance, in frail and unfit patients, and response, when present, is always really fast (median time to response: 2 months (r.1-6)), median OS from diagnosis was 94 months (range 21-234), median OS from start of pomalidomide was 9 months (range 1-25). Nine patients have surprisingly achieved a notable response (3 VGPR, 4 PR, 2 MR) after failure of novel agents (i.e. Carfilzomib, Daratumumab and Pomalidomide). Conclusions Pomalidomide-dexamethasone has shown significant efficacy and a very good compliance, thanks to oral administration, in a particularly severe setting of heavily pretreated patients, relapsed and refractory to all available therapeutic resources, also after failure of novel agents. Disclosures Lucchesi: Novartis: Honoraria; Pfizer: Honoraria; Incyte: Honoraria.

Intermittent Capecitabine Monotherapy with Lower Dose Intensity in Heavily Pretreated Patients with Metastatic Breast Cancer

2007 ◽  
Vol 93 (2) ◽  
pp. 129-132 ◽  
Author(s):  
Tomo Osako ◽  
Yoshinori Ito ◽  
Shunji Takahashi ◽  
Nahomi Tokudome ◽  
Takuji Iwase ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Metastatic Breast ◽  
Dose Intensity ◽  
Heavily Pretreated ◽  
Pretreated Patients

Adaptation of chemotherapy to the decline tumor markers in patients with poor prognosis nonseminomatous germ cell tumors:Real-world French experience.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 385-385
Author(s):  
Marion Rolland ◽  
Sara Faouzi ◽  
Leonor Chaltiel ◽  
Clement Dumont ◽  
Lionnel Geoffrois ◽  
...  
Keyword(s):  
Germ Cell ◽  
Tumor Marker ◽  
Tumor Markers ◽  
Poor Prognosis ◽  
Complete Response ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Cell Transplant ◽  
French Experience ◽  
Prognosis Group

385 Background: Personalized chemotherapy based on tumor marker decline is the new standard in poor prognosis germ-cell tumor in Europe since 2014 (GETUG 13, Lancet, Fizazi et al). The purpose of this study was to analyze the reproducibility of the princeps study in patients not selected in clinical routine between 2014 and 2018. Methods: Patients (pts) were eligible if they had at least one criteria of IGCCCG classification for poor prognosis group. They had to be treated according the study terms of GETUG 13 study and did not received prior treatment. They had to received 1 BEP (Bleomycin, Etoposide, Cisplatin). Tumor markers (HCG and AFP) were dosed between day 18 and 21. Then, they received 3 additional BEP if they had favorable tumor marker decline or intensive chemotherapy if they had unfavorable decline. Results: This retrospective study included 104 patients in 14 french centers treated between 2013 and 2018: 22,1 % (n = 23) in the favorable group (Fav), 77,9 % (n = 81) in the unfavorable group (Unfav). Thirty-two pts had PS ≥ 2. In Unfav, there were more pts with HCG > 50 000 UI/L (44,2 % vs 13 %, p = 0,0067), neutrophil-to-lymphocyt ratio was also higher (median 6,4 vs 4,5, p = 0,0199). At cycle 1, all pts received BEP in Fav and 87,5 % (n = 70) in Unfav. After chemotherapy and surgery, 65,2 % in Fav and 41,3 % in Unfav obtained complete response. At 30 months (median follow-up), Fav-OS was 80,5 % (IC95% 55,8 – 92,2) and Unfav-OS was 64,4 % (IC95% 52 – 74,4). At 30 months, rates were 69,6 % (IC95% 46,6 -84,2) and 63.5 % (IC95% 51,9 – 73) respectively. In GETUG 13 study, 3-years OS was 84 % in Fav and 73 % on Unfav; 3-years PFS was 70 % and 59 % respectively. Seven pts died because of toxicity in Unfav (No one in Fav). Neuropathy, anemia and thrombopenia were more frequent in Unfav. Salvage high-dose chemotherapy with stem-cell transplant was required in 4 (66,7 %) pts in Fav and 8 (36,4 %) pts in Unfav. Conclusions: This study showed a reproducibility of the princeps study in terms of PFS and OS. Toxicity seemed more important in real world. For the congress, results will be reported with 50 additional pts.

Phase I study of repeated cycles of high-dose cyclophosphamide, etoposide, and cisplatin administered without bone marrow transplantation.

1990 ◽  
Vol 8 (10) ◽  
pp. 1728-1738 ◽  
Author(s):  
J A Neidhart ◽  
W Kohler ◽  
C Stidley ◽  
A Mangalik ◽  
A Plauche ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Phase I ◽  
Performance Status ◽  
Complete Response ◽  
High Dose ◽  
Hematologic Toxicity ◽  
Tumor Type ◽  
Advanced Malignancy ◽  
Prior Therapy ◽  
And Performance

Forty-two patients with advanced malignancy judged unlikely to respond to standard treatment received high-dose combination chemotherapy with cyclophosphamide, etoposide, and cisplatin in a phase I trial. Twenty-two of these patients who had at least a partial response (PR) to the first cycle of therapy received a second cycle, and eight patients received three or more cycles of therapy. Bone marrow replacement was not used. The maximum-tolerated doses (MTDs) were cyclophosphamide 2.5 g/m2 on days 1 and 2; etoposide 500 mg/m2 on days 1, 2, and 3; and cisplatin 50 mg/m2 on days 1, 2, and 3. Hematologic toxicity was not dose-limiting by study design. Recovery to an absolute granulocyte count above 100/microL occurred at a median of 9 days from onset (range, 3 to 23 days) at the MTD. Recovery was delayed after the third cycle. Only one patient on his third cycle failed to recover peripheral blood counts and died of sepsis an day 43. Hematologic toxicity was not dose-dependent. Nonhematologic toxicities included emesis, fatigue, alopecia, diarrhea, and anorexia and were generally well tolerated. The dose-limiting toxicities were fatal pulmonary or cardiac toxicities in five of nine patients treated at the highest dose level. Patients likely to do well can be selected by tumor type, response to prior therapy, and performance status. Nine of 36 assessable patients had a complete response (CR) and 13 a PR for a response rate of 61%. Five patients (12%) remain alive and free of disease at 15 to 32 months. Repeated cycles of dose-intensive combination therapy can produce long-term disease-free remissions in patients with refractory tumor types. The toxicity of the regimen is acceptable if patients are carefully selected.

A phase I clinical and pharmacokinetic study of carboplatin and autologous bone marrow support.

1989 ◽  
Vol 7 (5) ◽  
pp. 651-661 ◽  
Author(s):  
T C Shea ◽  
M Flaherty ◽  
A Elias ◽  
J P Eder ◽  
K Antman ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Phase I ◽  
Autologous Bone Marrow ◽  
Recurrent Ovarian Cancer ◽  
Maximum Tolerated Dose ◽  
Pharmacokinetic Studies ◽  
Systemic Clearance ◽  
Heavily Pretreated ◽  
Pretreated Patients ◽  
Autologous Bone

A series of 33 patients were treated with a four-day continuous infusion of carboplatin in a phase I study to determine the maximum-tolerated dose (MTD) of this agent when used with autologous bone marrow reinfusion. Doses were escalated from 375 to 2,400 mg/m2; autologous bone marrow reinfusion was added to the regimen at doses of 1,600 mg/m2 and above. The MTD was determined to be 2,000 mg/m2. Dose-limiting toxicity consisting of reversible hepatotoxicity, renal dysfunction, and moderate to severe ototoxicity was observed with a dose of 2,400 mg/m2. There were ten responses in 31 heavily pretreated patients, including six responses in 11 patients with recurrent ovarian cancer. Pharmacokinetic studies revealed a systemic clearance (Clss) of 4.5 L/m2/h. This value is consistent with clearances reported for carboplatin administered at lower doses and by different schedules. No evidence for saturation of systemic clearance at higher doses was observed. Carboplatin appears to be an active drug that can undergo considerable dose escalation when used in conjunction with autologous bone marrow support.

Vinorelbine as a 96-Hour Continuous Infusion in Heavily Pretreated Patients with Metastatic Breast Cancer: A Cooperative Study by the GEICAM Group

2003 ◽  
Vol 3 (6) ◽  
pp. 399-404 ◽  
Author(s):  
Carlos Jara-Sánchez ◽  
Miguel Martín ◽  
Jose A. García-Sáenz ◽  
Agustí Barnadas ◽  
Antonio Fernández-Aramburo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Continuous Infusion ◽  
Metastatic Breast ◽  
Cooperative Study ◽  
Heavily Pretreated ◽  
Pretreated Patients

Phase I study of temozolomide in children and adolescents with recurrent solid tumors: a report from the Children's Cancer Group.

1998 ◽  
Vol 16 (9) ◽  
pp. 3037-3043 ◽  
Author(s):  
H S Nicholson ◽  
M Krailo ◽  
M M Ames ◽  
N L Seibel ◽  
J M Reid ◽  
...  
Keyword(s):  
Phase I ◽  
Children And Adolescents ◽  
Complete Response ◽  
Maximum Tolerated Dose ◽  
Hematologic Toxicity ◽  
Cancer Group ◽  
Grade 3 ◽  
Dose Levels ◽  
Dose Limiting Toxicity

PURPOSE The Children's Cancer Group conducted a phase I trial of temozolomide stratified by prior craniospinal irradiation (CSI). PATIENTS AND METHODS Children and adolescents with recurrent or progressive cancer were enrolled. Temozolomide was administered orally daily for 5 days, with subsequent courses administered every 21 to 28 days after full hematologic recovery. Dose levels tested included 100, 150, 180, 215, 245, and 260 mg/m2 daily. RESULTS Twenty-seven patients on the non-CSI stratum were assessable for hematologic toxicity. During the first three dose levels (100, 150, and 180 mg/m2 daily), only grades 1 and 2 hematologic toxicity occurred. One patient at 215 mg/m2 daily had grade 3 hematologic toxicity. Three of eight patients (38%) treated at 245 to 260 mg/m2 daily had dose-limiting toxicity (DLT), which included both neutropenia and thrombocytopenia. Twenty-two patients on the CSI stratum were assessable for hematologic toxicity. Hematologic DLT occurred in one of six patients (17%) at 100 mg/m2 daily and in two of four patients (50%) at 215 mg/m2 daily. No nonhematologic DLT occurred; nausea and vomiting occurred in more than half of the patients. After two courses of temozolomide, 10 patients had stable disease (SD), and three patients had a partial response (PR), one of whom subsequently had a complete response (CR) that persists through 24 months of follow-up. CONCLUSION The maximum-tolerated dose (MTD) of temozolomide for children and adolescents without prior CSI is 215 mg/m2 daily and for those with prior CSI is 180 mg/m2 daily for 5 days, with subsequent courses that begin on day 28. Temozolomide is well tolerated and should undergo phase II testing in children and adolescents.

Cisplatin, carboplatin, and cyclophosphamide combination chemotherapy in advanced-stage ovarian carcinoma: an Eastern Cooperative Oncology Group pilot study.

1991 ◽  
Vol 9 (10) ◽  
pp. 1793-1800 ◽  
Author(s):  
J Grem ◽  
P O'Dwyer ◽  
P Elson ◽  
N Simon ◽  
D Trump ◽  
...  
Keyword(s):  
Clinical Response ◽  
Response Rate ◽  
Residual Disease ◽  
Eastern Cooperative Oncology Group ◽  
Dose Intensity ◽  
Complete Response ◽  
Clinical Response Rate ◽  
Hematologic Toxicity ◽  
Survival Times ◽  
Moderate Nausea

Cyclophosphamide (CTX) 600 mg/m2, carboplatin 280 mg/m2, and cisplatin 50 mg/m2 were administered on day 1 every 4 weeks to 41 previously untreated ovarian cancer patients with residual disease greater than 2.0 cm after primary laparotomy. Of 22 patients with measurable disease treated with up to eight cycles of therapy, the overall clinical response rate was 73% (exact 95% confidence interval [CI], 50% to 89%), with 50% complete response (CR). Six of 11 clinical CR (cCR) patients underwent surgical restaging; three pathologic CRs (pCRs) and three pathologic partial responses (pPRs) with residual disease less than 2.0 cm were documented. Fourteen patients had nonmeasurable but assessable disease; the clinical response rate was 57% (Cl, 29% to 82%) with two (14%) CRs. Second-look surgery was performed in one of the two cCR patients; a pPR was documented. Five patients with nonassessable disease were stable during chemotherapy; two underwent surgery and had pCRs. The median time to treatment failure (TTF) was 14.8 months, and median survival for the 41 patients is 26.7 months. Overall, 37% of the patients had progression-free intervals of at least 2 years, and 27% have survival times in excess of 3 years. Hematologic toxicity was substantial but manageable, with 58% and 66% experiencing a granulocyte nadir less than 500/microL and a platelet nadir less than 50,000/microL, respectively. One treatment-associated fatality occurred as a result of leukopenic sepsis and renal failure in the setting of progressive disease and ureteral obstruction. Mild to moderate nausea and vomiting occurred in most patients, but none experienced severe ototoxicity or peripheral neuropathy. Over all courses, 73% of the projected dose intensity of CTX and carboplatin and 86% of cisplatin were delivered. Since granulocytopenia and thrombocytopenia were dose-limiting, the addition of colony-stimulating factors that support both myeloid and megakaryocyte precursors may permit further dose intensification.

Sign in / Sign up

Export Citation Format

Share Document