Asymptomatic decrease in LVEF Sample Clauses

Asymptomatic decrease in LVEF. The results of the LVEF assessments will be used to determine if trastuzumab and pertuzumab can be continued (see Table 5). · Echocardiogram is the preferred method for assessment of LVEF. However, LVEF assessment by MUGA scan is permitted. · All LVEF assessments should be performed by the same method (either echocardiogram or MUGA scan) that was performed at baseline. · Investigators are strongly urged to schedule the LVEF assessment at the same cardiac imaging facility that performed the patient's baseline LVEF assessment. Table 5. Trastuzumab and pertuzumab management based on LVEF assessments The following are instructions for patients who have an asymptomatic decrease in LVEF from baseline (prior to AC) to the LVEF assessment after Cycle 2 [before Cycle 3] of paclitaxel, trastuzumab, and pertuzumab. LVEF Asymptomatic decrease in LVEF percentage points from baseline Decrease of < 10 percentage points Decrease of ≥ 10 xxxxxxxxxx xxxxxx 0 50% Continue trastuzumab and pertuzumab Continue trastuzumab and pertuzumab 45-49% Continue trastuzumab and pertuzumab and repeat ECHO/MUGA in 3 weeks Discontinue trastuzumab and pertuzumab £ 45% Discontinue trastuzumab and pertuzumab
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Related to Asymptomatic decrease in LVEF

  • Increase in Limits If either Lessor or Lessee at any time deems the limits of the personal injury or property damage under the comprehensive public liability insurance then carried to be either excessive or insufficient, Lessor and Lessee shall endeavor in good faith to agree on the proper and reasonable limits for such insurance to be carried and such insurance shall thereafter be carried with the limits thus agreed on until further change pursuant to the provisions of this Article 13.

  • Increase in Total Commitment (a) The Company may from time to time, by written notice to the Administrative Agent (which shall deliver a copy thereof to each Lender), request that the Total Commitment be increased by an amount not to exceed the Incremental Facility Amount at such time. Such notice shall set forth the amount of the requested increase in the Total Commitment (which shall be an integral multiple of $10,000,000) and the date on which such increase is requested to become effective (which shall not be less than 10 Business Days or more than 60 days after the date of such notice), and shall offer to each Lender the opportunity to increase its Commitment by its Pro Rata Percentage of the proposed increased amount. Each Lender shall, by notice to the Company and the Administrative Agent given not more than 10 days after the date on which the Administrative Agent shall have delivered the Company's notice, either agree to increase its Commitment by all or a portion of the offered amount (each Lender so agreeing being an "Increasing Lender") or decline to increase its Commitment (and any Lender that does not deliver such notice within such period of 10 days shall be deemed to have declined to increase its Commitment) (each Lender so declining or being deemed to have declined being a "Non-Increasing Lender"). In the event that, on the 10th day after the Administrative Agent shall have delivered the Company's notice, the Lenders shall have agreed pursuant to the preceding sentence to increase their Commitments by an aggregate amount less than the increase in the Total Commitment requested by the Company, the Company may arrange for one or more banks or other financial institutions (any such bank or other financial institution referred to in this clause (a) being called an "Augmenting Lender"), which may include any Lender, to extend Commitments or increase their existing Commitments in an aggregate amount equal to the unsubscribed amount; provided that each Augmenting Lender, if not already a Lender hereunder, shall be subject to the approval of the Administrative Agent and the Company and each Augmenting Lender shall execute all such documentation as the Administrative Agent shall specify to evidence its Commitment and/or its status as a Lender hereunder. Any increase in the Total Commitment may be made in an amount which is less than the increase requested by the Company if the Company is unable to arrange for, or chooses not to arrange for, Augmenting Lenders.

  • Increase in Commitment At any time during the Commitment Increase Period, Borrower may request that Agent increase the Total Commitment Amount from the Closing Commitment Amount up to an amount that shall not exceed the Maximum Commitment Amount. Each such increase shall be in an amount of at least Ten Million Dollars ($10,000,000), increased by increments of One Million Dollars ($1,000,000), and may be made by either (i) proportionally increasing, for one or more Lenders, with their prior written consent, their respective Revolving Credit Commitments, or (ii) including one or more Additional Lenders, each with a new Revolving Credit Commitment, as a party to this Agreement (collectively, the “Additional Commitment”). During the Commitment Increase Period, the Lenders agree that Agent, in its sole discretion, may permit one or more Additional Commitments upon satisfaction of the following requirements: (A) each Additional Lender, if any, shall be an Eligible Transferee and shall execute an Additional Lender Assumption Agreement, (B) Agent shall provide to Borrower and each Lender a revised Schedule 1 to this Agreement, including revised Commitment Percentages for each of the Lenders, if appropriate, at least three Business Days prior to the effectiveness of such Additional Commitments (each an “Additional Lender Assumption Effective Date”), and (C) Borrower shall execute and deliver to Agent and the Lenders such replacement or additional Revolving Credit Notes as shall be required by Agent (and requested by the Lenders). The Lenders hereby authorize Agent to execute each Additional Lender Assumption Agreement on behalf of the Lenders. On each Additional Lender Assumption Effective Date, the Lenders shall make adjustments among themselves with respect to the Revolving Loans then outstanding and amounts of principal, interest, facility fees, utilization fees and other amounts paid or payable with respect thereto as shall be necessary, in the opinion of Agent, in order to reallocate among such Lenders such outstanding amounts, based on the revised Commitment Percentages and to otherwise carry out fully the intent and terms of this Section 2.9(b). Borrower shall not request any increase in the Commitment pursuant to this Section 2.9(b) if a Default or an Event of Default shall then exist, or immediately after giving effect to any such increase would exist.

  • INCREASE IN RETENTION A. If the Ceding Company should increase the retention limits as listed in Exhibit II, prompt written notice of the increase must be given to the Reinsurer.

  • Increase in Revolving Commitments (a) The Borrower may, by written notice to the Administrative Agent from time to time, request that the total Revolving Commitment be increased by an aggregate amount not to exceed the Incremental Revolving Facility Amount at such time. Upon the receipt of such request by the Administrative Agent, the Administrative Agent shall deliver a copy thereof to each Revolving Lender. Such notice shall set forth the amount of the requested increase (which shall be in minimum increments of $500,000 and a minimum amount of $2,500,000 or equal to the remaining Incremental Revolving Facility Amount) and the date on which such increase is requested to become effective (which shall be not less than 10 Business Days nor more than 60 days after the date of such notice and which, in any event, must be prior to the Revolving Credit Maturity Date), and shall offer each Revolving Lender the opportunity to increase its Revolving Commitment by its Pro Rata Percentage of the proposed increased amount. Each Revolving Lender shall, by notice to the Borrower and the Administrative Agent given not more than 10 days after the date of the Administrative Agent’s notice, either agree to increase its Revolving Commitment by all or a portion of the offered amount (each Revolving Lender so agreeing being an “Increasing Revolving Lender”) or decline to increase its Revolving Commitment (and any Revolving Lender that does not deliver such a notice within such period of 10 days shall be deemed to have declined to increase its Revolving Commitment) (each Revolving Lender so declining or being deemed to have declined being a Non-Increasing Revolving Lender”). In the event that, on the 10th day after the Administrative Agent shall have delivered a notice pursuant to the second sentence of this paragraph, the Increasing Revolving Lenders shall have agreed pursuant to the preceding sentence to increase their Revolving Commitments by an aggregate amount less than the increase requested by the Borrower, such Borrower may arrange for one or more banks or other entities (any such bank or other entity being called an “Augmenting Revolving Lender”), which may include any Lender, to extend Revolving Commitments or increase their existing Revolving Commitments in an aggregate amount equal to the unsubscribed amount; provided, however, that each Augmenting Revolving Lender shall be subject to the prior written approval of the Administrative Agent, the Swingline Lender and the Issuing Bank (which approvals shall not be unreasonably withheld or delayed), and the Borrower and each Augmenting Revolving Lender shall execute all such documentation as the Administrative Agent shall reasonably specify to evidence its Revolving Commitment and/or its status as a Revolving Lender hereunder, Any such increase may be made in an amount that is less than the increase requested by the Borrower if such Borrower is unable to arrange for, or chooses not to arrange for, Augmenting Revolving Lenders.

  • Increase in Aggregate Commitment The Borrowers may, at their option, on up to two occasions, seek to increase the Aggregate Commitment by up to an aggregate amount of $300,000,000 (resulting in a maximum Aggregate Commitment of $600,000,000) upon at least three (3) Business Days’ written notice to the Agent, which notice shall specify the amount of such increase and shall be delivered at a time when no Default or Unmatured Default has occurred and is continuing. The Borrowers may, after giving such notice, offer the increase in the Aggregate Commitment on either a ratable basis to the Lenders or on a non-pro rata basis to one or more Lenders and/or to other banks or entities reasonably acceptable to the Agent. No increase in the Aggregate Commitment shall become effective until the existing or new Lenders extending such incremental Commitment amount and the Borrowers shall have delivered to the Agent a document in form reasonably satisfactory to the Agent pursuant to which any such existing Lender states the amount of its Commitment increase, any such new Lender states its Commitment amount and agrees to assume and accept the obligations and rights of a Lender hereunder and the Borrowers accept such incremental Commitments. The Lenders (new or existing) shall accept an assignment from the existing Lenders, and the existing Lenders shall make an assignment to the new or existing Lender accepting a new or increased Commitment, of an interest in each then outstanding Ratable Advance such that, after giving effect thereto, all Ratable Advances are held ratably by the Lenders in proportion to their respective Commitments. Assignments pursuant to the preceding sentence shall be made in exchange for the principal amount assigned plus accrued and unpaid interest, Commitment Fees and Facility Fees. The Borrowers shall make any payments under Section 3.4 resulting from such assignments.

  • Increase in Commitments At any time following the Agreement Date and prior to the Termination Date the aggregate amount of the Commitments may, at the option of the Borrower, be increased by an amount not in excess of $200,000,000, either by new Banks establishing such additional Commitments or by one or more then-existing Banks increasing their Commitments (each such increase by either means, a "Commitment Increase," and each such new Bank or Bank increasing its Commitment, an "Additional Commitment Bank"); provided that (a) each Additional Commitment Bank shall be reasonably acceptable to the Administrative Agent and the Issuing Bank, (b) no Default shall exist immediately prior to or after the effective date of such Commitment Increase, (c) each such Commitment Increase shall be in an amount not less than $10,000,000 and multiples of $5,000,000 in excess thereof, (d) no such Commitment Increase shall become effective unless and until the Borrower, the Administrative Agent, the Issuing Bank and the Additional Commitment Banks shall have executed and delivered an agreement substantially in the form of Schedule 1.09 (a "Commitment Increase Supplement"), and (d) the increase in the Total Commitments shall not exceed $200,000,000. On the effective date of such Commitment Increase, each Additional Commitment Bank shall purchase, for assignment, from each other existing Bank the portion of such other Bank's RC Loans and Letter of Credit Participations outstanding at such time such that, after giving effect to such assignments, the respective aggregate amount of RC Loans and Letter of Credit Participations of each Bank shall be equal to such Bank's pro rata share (based on the total Commitments, as increased pursuant hereto) of the aggregate RC Loans and Letter of Credit Participations outstanding. The purchase price for the RC Loans and Letter of Credit Participations so assigned shall be the principal amount of the RC Loans and unreimbursed Drawings so assigned plus the amount of accrued and unpaid interest thereon on the date of assignment. Upon payment of such purchase price, each other Bank shall be automatically deemed to have sold and made such an assignment to such Additional Commitment Bank and shall, to the extent of the interest assigned, be released from its obligations under this Agreement, and such Additional Commitment Bank shall be automatically deemed to have purchased and assumed such an assignment from each other Bank and, if not already a Bank hereunder, shall be a party hereto and, to the extent of the interest assigned, have the rights and obligations of a Bank under this Agreement.

  • Increase of Commitments; Additional Lenders (a) From time to time after the Closing Date and in accordance with this Section, the Borrower and one or more Increasing Lenders or Additional Lenders (each as defined below) may enter into an agreement to increase the aggregate Revolving Commitments hereunder (each such increase, an “Incremental Commitment”) so long as the following conditions are satisfied:

  • Reallocation of Applicable Revolving Percentages to Reduce Fronting Exposure All or any part of such Defaulting Lender’s participation in L/C Obligations and Swingline Loans shall be reallocated among the Non-Defaulting Lenders in accordance with their respective Applicable Revolving Percentages (calculated without regard to such Defaulting Lender’s Commitment) but only to the extent that such reallocation does not cause the aggregate Revolving Exposure of any Non-Defaulting Lender to exceed such Non-Defaulting Lender’s Revolving Commitment. Subject to Section 11.20, no reallocation hereunder shall constitute a waiver or release of any claim of any party hereunder against a Defaulting Lender arising from that Lender having become a Defaulting Lender, including any claim of a Non-Defaulting Lender as a result of such Non-Defaulting Lender’s increased exposure following such reallocation.

  • Reallocation of Applicable Percentages to Reduce Fronting Exposure During any period in which there is a Defaulting Lender, for purposes of computing the amount of the obligation of each non-Defaulting Lender to acquire, refinance or fund participations in Letters of Credit or Swing Line Loans pursuant to Sections 2.03 and 2.04, the “Applicable Percentage” of each non-Defaulting Lender shall be computed without giving effect to the Commitment of that Defaulting Lender; provided, that, (i) each such reallocation shall be given effect only if, at the date the applicable Lender becomes a Defaulting Lender, no Default or Event of Default exists; and (ii) the aggregate obligation of each non-Defaulting Lender to acquire, refinance or fund participations in Letters of Credit and Swing Line Loans shall not exceed the positive difference, if any, of (1) the Commitment of that non-Defaulting Lender minus (2) the aggregate Outstanding Amount of the Committed Loans of that Lender.

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