Carboplatin-containing Regimens Research Articles

Role of Non-Platinum-Based Chemotherapy in Advanced Non-Small Cell Lung Cancer

Platinum-based chemotherapy regimens have been the mainstay of systemic chemotherapy in advanced NSCLC. However, substantial toxicity impairs the survival and symptom control advantages of cisplatin- and even carboplatin-containing regimens. With the advent of newer active agents in the 1990s, investigators began conducting clinical studies with the aim of potentially eliminating platinum from initial therapy for patients with advanced NSCLC. Conceptually, three major hypotheses were tested in phase III trials: (i) single, non-platinum agents are equal in efficacy to platinum in combination with these agents; (ii) non-platinum combinations are potentially more effective than platinum-based therapy; and (iii) non-platinum combinations are at least equally efficacious, but less toxic than, platinum-based therapy. An overall analysis of phase III data indicates that combinations of these newer agents with platinum are superior to the single agent alone and that combinations of non-platinum agents are no more effective than platinum-based therapy. Non-platinum therapy has a different and perhaps marginally improved toxicity spectrum compared with platinum-based therapy. In the few studies utilizing a formal quality-of-life analysis, no differences have been detected. Therefore, while several non-platinum regimens have been validated in phase III trials as reasonable alternatives to platinum-based therapy, they have not been proven to be clearly superior.

An ex vivo chemoresponse assay predicts carboplatin-induced progression-free interval in ovarian cancer

5134 Background: Carboplatin is the mainstay of primary ovarian cancer and is often used in recurrent ovarian cancer. The ability to identify tumors that will respond to this drug prior to selection of therapy would allow patients to avoid ineffective treatments and should lead to an improvement in outcome. Methods: We evaluated an ex vivo chemoresponse assay in predicting progression-free interval (PFI) in patients with ovarian cancer in response to Carboplatin-containing regimens. 128 women with primary or recurrent ovarian carcinoma, who were subsequently treated with a Carboplatin-containing regimen, had tumors tested with an ex vivo chemoresponse assay between 4/30/1997 and 4/30/2002. The assay results were scored for sensitivity or resistance based on live cell number after exposure to varied concentrations of Carboplatin. PFI and assay results were linked by an independent contract research organization. Cox Proportional Hazard Model analysis was used to identify independent prognostic factors. Results: Results of the Carboplatin assays for these patients were a significant independent predictor of PFI (p=0.049, Hazard Ratio (HR) of cases with a Resistant assay result vs. a Sensitive assay result (HRR-S)=2.52 [95% CI: 1.01 to 6.30], HR of patients with a Resistant assay result vs. an Intermediate assay result (HRR-I)=1.59 [95% CI: 1.00 to 2.51]). Further, the predictive accuracy of the assay improved as process improvements were implemented: 70 primary assays before 1/1/2001 were suggestive (p=0.16, HRR-S=2.60 [95% CI: 0.69 to 9.86]); whereas 43 primary assays since 1/1/2001 were significant (p=0.048, HRR-S =4.58 [95% CI: 1.01 to 20.80]). Conclusion: These data demonstrate the utility of an ex vivo chemoresponse assay in predicting the clinical outcome of ovarian cancer patients treated with Carboplatin-containing regimens. Moreover, continuous quality improvements enhanced the efficacy of the ex vivo chemoresponse assay. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Precision Therapeutics, Inc. Precision Therapeutics, Inc. Precision Therapeutics, Inc.

An ex vivo chemoresponse assay predicts carboplatin-induced progression-free interval in ovarian cancer

5134 Background: Carboplatin is the mainstay of primary ovarian cancer and is often used in recurrent ovarian cancer. The ability to identify tumors that will respond to this drug prior to selection of therapy would allow patients to avoid ineffective treatments and should lead to an improvement in outcome. Methods: We evaluated an ex vivo chemoresponse assay in predicting progression-free interval (PFI) in patients with ovarian cancer in response to Carboplatin-containing regimens. 128 women with primary or recurrent ovarian carcinoma, who were subsequently treated with a Carboplatin-containing regimen, had tumors tested with an ex vivo chemoresponse assay between 4/30/1997 and 4/30/2002. The assay results were scored for sensitivity or resistance based on live cell number after exposure to varied concentrations of Carboplatin. PFI and assay results were linked by an independent contract research organization. Cox Proportional Hazard Model analysis was used to identify independent prognostic factors. Results: Results of the Carboplatin assays for these patients were a significant independent predictor of PFI (p=0.049, Hazard Ratio (HR) of cases with a Resistant assay result vs. a Sensitive assay result (HRR-S)=2.52 [95% CI: 1.01 to 6.30], HR of patients with a Resistant assay result vs. an Intermediate assay result (HRR-I)=1.59 [95% CI: 1.00 to 2.51]). Further, the predictive accuracy of the assay improved as process improvements were implemented: 70 primary assays before 1/1/2001 were suggestive (p=0.16, HRR-S=2.60 [95% CI: 0.69 to 9.86]); whereas 43 primary assays since 1/1/2001 were significant (p=0.048, HRR-S =4.58 [95% CI: 1.01 to 20.80]). Conclusion: These data demonstrate the utility of an ex vivo chemoresponse assay in predicting the clinical outcome of ovarian cancer patients treated with Carboplatin-containing regimens. Moreover, continuous quality improvements enhanced the efficacy of the ex vivo chemoresponse assay. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Precision Therapeutics, Inc. Precision Therapeutics, Inc. Precision Therapeutics, Inc.

Combination Regimen with Carboplatin, Epirubicin and Etoposide in Metastatic Carcinomas of Unknown Primary Site: A Hellenic Co-Operative Oncology Group Phase II Study

The encouraging results that have been reported for cisplatin combination chemotherapy in a minority of patients with cancer of unknown primary (CUP) together with the previously shown equal activity of carboplatin in this setting, prompted us to investigate the effectiveness of a carboplatin-containing regimen in a phase II clinical trial.Sixty-two evaluable CUP patients entered the protocol. The chemotherapy regimen consisted of carboplatin 300 mg/m² IV D₁, epirubicin 45 mg/m² IV D₁ and etoposide 120 mg/m² IV D_1–3 (CEE regimen) administered every 3 weeks. The median age of the patients was 61 years and 36 were male. Thirty-one diagnosed as poorly differentiated carcinomas (pdc) and the rest as adenocarcinomas. By clinicopathological criteria, 14 patients had a predominately nodal disease with pdc or poorly differentiated adenocarcinomas (pda), 3 women peritoneal carcinomatosis, and the remaining 46 patients had a predominately splanchnic involvement (24 pdc, 22 pda). Twenty-three patients responded to chemotherapy with 4 (6.5%) complete and 19 (30.5%) partial responders (RR 37%, 95% CI 25–49%). An equal activity of the regimen was observed between the two major histopathological types, the pdc and the adenocarcinomas. Nevertheless, significant differences were seen when the CEE regimen was assessed for its activity in the distinct clinicopathological subsets of CUP. Patients with predominately nodal disease of midline distribution with pdc or pda, and women with peritoneal carcinomatosis, achieved a response rate of 64 and 62% respectively, as compared with a 26% response rate for those with predominately splanchnic involvement. Overall median survival was 10 months and for patients with midline distribution 15 months. The regimen was well tolerated. It is concluded that CEE is a relatively nontoxic chemotherapy regimen and easily administered on an outpatient basis. This prospective phase II study confirmed the activity of carboplatin in the chemosensitive subsets of the predominately nodal disease of midline distribution and peritoneal carcinomatosis in women in the CUP syndrome.

Renal disorders with a carboplatin-containing anticancer regimen

Renal disorders with a carboplatin-containing anticancer regimen

Comparison between a cisplatin-containing regimen and a carboplatin-containing regimen for recurrent or metastatic bladder cancer patients: A randomized phase II study

The aim of this randomized Phase II study was to compare the efficacy and toxicity of a cisplatin-containing regimen with a carboplatin-containing regimen for patients with recurrent or metastatic bladder cancer. Fifty-seven patients with recurrent or metastatic bladder cancer were randomized to receive M-VEC treatment (methotrexate, vinblastine, epirubicin, and cisplatin) (n = 29) or M-VECa treatment (methotrexate, vinblastine, epirubicin, and carboplatin) (n = 28). The chemotherapy was scheduled at 28-day intervals. Recombinant granulocyte-colony stimulating factors were administered daily when the absolute neutrophil count fell below 1000/mm3. The development of ototoxicity was evaluated by measuring auditory brain stem response. Of the 57 entered patients, 55 were evaluable for response and toxicity. The overall clinical response rate was 71% (with 25% complete responses) in the M-VEC group and 41% (with 11% complete responses) in the M-VECa group (P = 0.04). M-VEC chemotherapy was associated with more pronounced side effects. There was a statistically significant difference between M-VEC and M-VECa in terms of gastrointestinal toxicity (P = 0.04), nephrotoxicity (P = 0.03), and neurotoxicity (P = 0.02) during Cycle 3 of chemotherapy. Leukopenia and neutropenia were worse in the M-VECa arm, but not significantly so (P = 0.4). Ototoxicity was only detected in one of seven examined M-VEC patients after two cycles of chemotherapy. M-VECa has a low level of gastrointestinal, renal, neurologic, and otologic toxicity, but is apparently less effective than M-VEC in the treatment of recurrent or metastatic bladder cancer. However, a larger, randomized Phase III trial is needed to confirm these results.

Docetaxel in stage III and IV non-small cell lung cancer

Phase II studies have been conducted to evaluate the efficacy and tolerability of docetaxel in the treatment of patients with advanced non-small cell lung cancer (NSCLC). Docetaxel was administered to patients with stage III and IV NSCLC at a dose of 100 mg/m2 intravenously over 1 h every 3 weeks. Patients included in these four phase II studies had received either no prior chemotherapy (n = 114) or treatment with cisplatin- or carboplatin-containing regimens (n = 57). Major objective response rates were reported in 33-38% of previously untreated evaluable patients and in 21-27% of previously treated evaluable patients. Neutropenia was the most common adverse event. Non-haematological adverse events included hypersensitivity reactions, skin rash, alopecia and fluid retention. Docetaxel demonstrates significant antitumour activity in patients with advanced NSCLC. Further investigations of this agent with corticosteroid premedication, colony-stimulating factors and other agents active in NSCLC are indicated.

Cancer in Women: Trends in Care

Breast cancer, ovarian cancer, and cervical cancer are neoplastic diseases of primary concern to women. Breast cancer alone will afflict up to 12% of all women. Early detection and treatment of this disease can account for relatively stable mortality rates in the face of increased incidence. Identification of prognostic factors as well as extensive staging of the disease have been important developments in identifying treatment strategies for breast cancer. Advancements in early detection, breast-conserving surgery, and adjuvant systemic therapy have had a major impact on the treatment of this disease. The principle treatment for both ovarian cancer and cervical cancer is surgery. A large number of patients with ovarian cancer have evidence of metastatic intra-abdominal disease at the time of staging laparotomy. These patients are candidates for chemotherapy, generally with cisplatin- or carboplatin-containing regimens. Intraperitoneal administration of chemotherapy drugs has been used to consolidate therapy or to treat residual therapy in the abdomen. Further development of new and effective drugs such as the new compound Taxol (Bristol-Meyers Squibb) are needed to further enhance the treatment of this disease. Cervical cancer, on the other hand, is largely curative by surgical procedures. Early detection and treatment has had a major impact on the mortality incidence of this disease. However, there are a small number of patients who have metastatic disease at the time of diagnosis or a small subset of patients who fail to respond to curative surgery. These patients are likewise candidates for chemotherapy. The activity of existing regimens has been limited, and there is a need for the identification and development of more active compounds.

Comparison of two carboplatin-containing regimens with standard chemotherapy for small cell lung cancer in a randomized phase II study : Postmus PE, Splinter TAW, Palmen FMLHG, Carney DN, Festen J, Burghouts JThW et al. Department of Pulmonary Diseases, University Hospital, Oostersingel 59, 9713 EZ Groningen. Eur J Cancer 1992;28:96–100

Comparison of two carboplatin-containing regimens with standard chemotherapy for small cell lung cancer in a randomized phase II study : Postmus PE, Splinter TAW, Palmen FMLHG, Carney DN, Festen J, Burghouts JThW et al. Department of Pulmonary Diseases, University Hospital, Oostersingel 59, 9713 EZ Groningen. Eur J Cancer 1992;28:96–100

Comparison of two carboplatin-containing regimens with standard chemotherapy for small cell Lung Cancer in a randomised phase II study

The EORTC Lung Cancer Cooperative group performed a randomised phase II study in patients with small cell lung cancer comparing the standard cyclophosphamide/doxorubicin/etoposide (CDE) regimen with two regimens containing the new and active cisplatin derivative, carboplatin, 400 mg/m 2 in combination with ifosfamide, a drug without important myelotoxicity, at a dose of 5 g/m 2 (IMP) or the non-myelotoxic drug vincristine twice 2 mg (VP). Of 178 evaluable patients, 63 received CDE [30 limited disease (LD), 33 extensive disease (ED)], 55 received IMP (22 LD, 33 ED) and 60 (26 LD, 34 ED) were treated with VP. The response duration was not statistically different: CDE 31 weeks, IMP 29 weeks and VP 21 weeks. The time to progression after CDE was 28 weeks, IMP 24 weeks and VP 17 weeks. This was significantly shorter after VP than after CDE ( P = 0.017). The 60% response rate of the VP combination was low compared with CDE (83%) and IMP (77%). Toxicity of all three regimens was acceptable, and dose reduction for myelosuppression was necessary in only a minority of the patients. We conclude from this study that the combination of carboplatin, at the maximally tolerated dose of 400 mg/m 2, in combination with ifosfamide 5 g/m 2, is an active regimen with efficacy comparable with the standard CDE regimen.

Two carboplatin-containing regimens for small cell lung cancer: preliminary results of a randomized phase II trial

Two carboplatin-containing regimens for small cell lung cancer: preliminary results of a randomized phase II trial